Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
January-2023 Volume 27 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
January-2023 Volume 27 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML

  • Supplementary Files
    • Supplementary_Data.pdf
Article Open Access

Inhibition of colorectal cancer tumorigenesis by ursolic acid and doxorubicin is mediated by targeting the Akt signaling pathway and activating the Hippo signaling pathway

  • Authors:
    • Dan Hu
    • Ruo Yu Meng
    • Thi Van Nguyen
    • Ok Hee Chai
    • Byung Hyun Park
    • Ju-Seog Lee
    • Soo Mi Kim
  • View Affiliations / Copyright

    Affiliations: Department of Physiology, Jeonbuk National University Medical School, Jeonju, Jeollabuk‑do 54907, Republic of Korea, Department of Physiology, Jeonbuk National University Medical School, Jeonju, Jeollabuk‑do 54907, Republic of Korea, Department of Anatomy, Jeonbuk National University Medical School, Jeonju, Jeollabuk‑do 54907, Republic of Korea, Department of Anatomy, Jeonbuk National University Medical School, Jeonju, Jeollabuk‑do 54907, Republic of Korea, Department of Biochemistry, Jeonbuk National University Medical School, Jeonju, Jeollabuk‑do 54907, Republic of Korea, Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 11
    |
    Published online on: November 15, 2022
       https://doi.org/10.3892/mmr.2022.12898
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Colorectal cancer (CRC) is one of the deadliest malignant tumors worldwide and its prevalence is increasing in South Korea. The efficacy of combined treatment with natural product‑derived and chemotherapy agents including curcumin combined with 5‑fluorouracil, resveratrol combined with cisplatin and epigallocatechin‑3‑gallate (EGCG) combined with cisplatin in preventing cancer progression and killing cancer cells has emerged. The Akt and Hippo signaling pathways serve a key role in colorectal tumor growth; however, the exact role of the crosstalk between Akt and Hippo signaling pathways in CRC remains poorly elucidated. The combined effect of UA and DOX on the cell proliferation, apoptosis, migration and cell cycle of CRC cells were investigated by performing Cell proliferation assay, a soft agar colony formation assay, flow cytometry, wound healing assay and western blotting assay. Subsequently, the expression of AKT and Hippo signaling pathway‑associated proteins were also assessed by western blot assay. Moreover, a xenograft nude mouse model was constructed to verify the effects of UA and DOX on the tumorigenesis of HCT116 cell in vivo. The present study reported that ursolic acid (UA) strongly enhanced the antitumor action of doxorubicin (DOX) via blocking the Akt/glycogen synthase kinase‑3β (Gsk3β) signaling pathway and activating tumor‑suppressive Hippo signaling (mammalian Ste20‑like kinase 1 and 2, salvador family WW domain containing protein 1 and MOB kinase activator 1), thereby downregulating downstream effector yes‑associated protein 1 (Yap) and connective tissue growth factor (CTGF) protein expression levels in CRC cells. Furthermore, The PI3K inhibitor LY294002 further suppressed Akt activity and enhance the function of Hippo pathway‑associated proteins in DOX + UA treated cells; this effect led to subsequent oncogenic Yap and CTGF inhibition following combined treatment, whereas Akt activator SC79 exerted an opposite effect in CTGF expression. In vivo, treatment with UA combined with DOX markedly suppressed the progression of CRC without any toxic effects on a xenograft mouse model by disrupting Akt signaling and activating the Hippo signaling pathway. These results demonstrated that UA and DOX treatment successfully induced Akt/Gsk3β inactivation via Hippo signaling pathway activation to promote Yap degradation, resulting in the inhibition of colorectal tumorigenesis. In conclusion, these findings suggested that combination therapy with UA and DOX may be more effective than DOX alone. UA may be a novel anticancer strategy and could be considered for investigation as a complementary chemotherapy agent in the future.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global patterns and trends in colorectal cancer incidence and mortality. Gut. 66:683–691. 2017. View Article : Google Scholar : PubMed/NCBI

2 

Shin DW, Chang D, Jung JH, Han K, Kim SY, Choi KS, Lee WC and Park JH and Park JH: Disparities in the participation rate of colorectal cancer screening by fecal occult blood test among people with disabilities: A national database study in South Korea. Cancer Res Treat. 52:60–73. 2020. View Article : Google Scholar : PubMed/NCBI

3 

Yang SY, Cho MS and Kim NK: Difference between right-sided and left-sided colorectal cancers: From embryology to molecular subtype. Expert Rev Anticancer Ther. 18:351–358. 2018. View Article : Google Scholar : PubMed/NCBI

4 

McQuade RM, Stojanovska V, Bornstein JC and Nurgali K: Colorectal cancer chemotherapy: The evolution of treatment and new approaches. Curr Med Chem. 24:1537–1557. 2017. View Article : Google Scholar : PubMed/NCBI

5 

Cargnin ST and Gnoatto SB: Ursolic acid from apple pomace and traditional plants: A valuable triterpenoid with functional properties. Food Chem. 220:477–489. 2017. View Article : Google Scholar : PubMed/NCBI

6 

Xu C, Liao Y, Fang C, Tsunoda M, Zhang Y, Song Y and Deng S: Simultaneous analysis of ursolic acid and oleanolic acid in guava leaves using QuEChERS-based extraction followed by high-performance liquid chromatography. J Anal Methods Chem. 2017:29845622017. View Article : Google Scholar : PubMed/NCBI

7 

Zheng JL, Wang SS, Shen KP, Huang XW, Li M, Chen L, Peng X, An HM and Hu B: Ursolic acid potentiated oxaliplatin to induce apoptosis in colorectal cancer RKO cells. Pharmazie. 75:246–249. 2020.PubMed/NCBI

8 

Wang X, Wang T, Yi F, Duan C, Wang Q, He N, Zhu L, Li Q and Deng W: Ursolic acid inhibits tumor growth via epithelial-to-mesenchymal transition in colorectal cancer cells. Biol Pharm Bull. 42:685–691. 2019. View Article : Google Scholar : PubMed/NCBI

9 

Cai Q, Lin J, Zhang L, Lin J, Wang L, Chen D and Peng J: Comparative proteomics-network analysis of proteins responsible for ursolic acid-induced cytotoxicity in colorectal cancer cells. Tumour Biol. 39:10104283176950152017. View Article : Google Scholar : PubMed/NCBI

10 

Wang C, Shu L, Zhang C, Li W, Wu R, Guo Y, Yang Y and Kong AN: Histone methyltransferase Setd7 regulates Nrf2 signaling pathway by phenethyl isothiocyanate and ursolic acid in human prostate cancer cells. Mol Nutr Food Res. 62:e17008402018. View Article : Google Scholar : PubMed/NCBI

11 

Yang K, Chen Y, Zhou J, Ma L, Shan Y, Cheng X, Wang Y, Zhang Z, Ji X, Chen L, et al: Ursolic acid promotes apoptosis and mediates transcriptional suppression of CT45A2 gene expression in non-small-cell lung carcinoma harbouring EGFR T790M mutations. Br J Pharmacol. 176:4609–4624. 2019. View Article : Google Scholar : PubMed/NCBI

12 

Mendes VIS, Bartholomeusz GA, Ayres M, Gandhi V and Salvador JAR: Synthesis and cytotoxic activity of novel A-ring cleaved ursolic acid derivatives in human non-small cell lung cancer cells. Eur J Med Chem. 123:317–331. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Chan EWC, Soon CY, Tan JBL, Wong SK and Hui YW: Ursolic acid: An overview on its cytotoxic activities against breast and colorectal cancer cells. J Integr Med. 17:155–160. 2019. View Article : Google Scholar : PubMed/NCBI

14 

Kim K, Shin EA, Jung JH, Park JE, Kim DS, Shim BS and Kim SH: Ursolic acid induces apoptosis in colorectal cancer cells partially via upregulation of MicroRNA-4500 and inhibition of JAK2/STAT3 phosphorylation. Int J Mol Sci. 20:1142018. View Article : Google Scholar : PubMed/NCBI

15 

Prasad S, Yadav VR, Sung B, Reuter S, Kannappan R, Deorukhkar A, Diagaradjane P, Wei C, Baladandayuthapani V, Krishnan S, et al: Ursolic acid inhibits growth and metastasis of human colorectal cancer in an orthotopic nude mouse model by targeting multiple cell signaling pathways: Chemosensitization with capecitabine. Clin Cancer Res. 18:4942–4953. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Liu P, Du R and Yu X: Ursolic acid exhibits potent anticancer effects in human metastatic melanoma cancer cells (SK-MEL-24) via apoptosis induction, inhibition of cell migration and invasion, cell cycle arrest, and inhibition of mitogen-activated protein kinase (MAPK)/ERK signaling pathway. Med Sci Monit. 25:1283–1290. 2019. View Article : Google Scholar : PubMed/NCBI

17 

Liu T, Ma H, Shi W, Duan J, Wang Y, Zhang C, Li C, Lin J, Li S, Lv J and Lin L: Inhibition of STAT3 signaling pathway by ursolic acid suppresses growth of hepatocellular carcinoma. Int J Oncol. 51:555–562. 2017. View Article : Google Scholar : PubMed/NCBI

18 

Zhang L, Cai QY, Liu J, Peng J, Chen YQ, Sferra TJ and Lin JM: Ursolic acid suppresses the invasive potential of colorectal cancer cells by regulating the TGF-β1/ZEB1/miR-200c signaling pathway. Oncol Lett. 18:3274–3282. 2019.PubMed/NCBI

19 

Cheng J, Liu Y, Liu Y, Liu D, Liu Y, Guo Y, Wu Z, Li H and Wang H: Ursolic acid alleviates lipid accumulation by activating the AMPK signaling pathway in vivo and in vitro. J Food Sci. 85:3998–4008. 2020. View Article : Google Scholar : PubMed/NCBI

20 

Kim GH, Kan SY, Kang H, Lee S, Ko HM, Kim JH and Lim JH: Ursolic acid suppresses cholesterol biosynthesis and exerts anti-cancer effects in hepatocellular carcinoma cells. Int J Mol Sci. 20:47672019. View Article : Google Scholar : PubMed/NCBI

21 

Lin CW, Chin HK, Lee SL, Chiu CF, Chung JG, Lin ZY, Wu CY, Liu YC, Hsiao YT, Feng CH, et al: Ursolic acid induces apoptosis and autophagy in oral cancer cells. Environ Toxicol. 34:983–991. 2019. View Article : Google Scholar : PubMed/NCBI

22 

Lin JH, Chen SY, Lu CC, Lin JA and Yen GC: Ursolic acid promotes apoptosis, autophagy, and chemosensitivity in gemcitabine-resistant human pancreatic cancer cells. Phytother Res. 34:2053–2066. 2020. View Article : Google Scholar : PubMed/NCBI

23 

Lin W and Ye H: Anticancer activity of ursolic acid on human ovarian cancer cells via ROS and MMP mediated apoptosis, cell cycle arrest and downregulation of PI3K/AKT pathway. J BUON. 25:750–756. 2020.PubMed/NCBI

24 

Li W, Zhang H, Nie M, Tian Y, Chen X, Chen C, Chen H and Liu R: Ursolic acid derivative FZU-03,010 inhibits STAT3 and induces cell cycle arrest and apoptosis in renal and breast cancer cells. Acta Biochim Biophys Sin (Shanghai). 49:367–373. 2017. View Article : Google Scholar : PubMed/NCBI

25 

Ruan JS, Zhou H, Yang L, Wang L, Jiang ZS, Sun H and Wang SM: Ursolic acid attenuates TGF-β1-induced epithelial-mesenchymal transition in NSCLC by targeting integrin αVβ5/MMPs signaling. Oncol Res. 27:593–600. 2019. View Article : Google Scholar : PubMed/NCBI

26 

Sohn EJ, Won G, Lee J, Yoon SW, Lee I, Kim HJ and Kim SH: Blockage of epithelial to mesenchymal transition and upregulation of let 7b are critically involved in ursolic acid induced apoptosis in malignant mesothelioma cell. Int J Biol Sci. 12:1279–1288. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Lee NR, Meng RY, Rah SY, Jin H, Ray N, Kim SH, Park BH and Kim SM: Reactive oxygen species-mediated autophagy by ursolic acid inhibits growth and metastasis of esophageal cancer cells. Int J Mol Sci. 21:94092020. View Article : Google Scholar : PubMed/NCBI

28 

Park HJ, Jo DS, Choi DS, Bae JE, Park NY, Kim JB, Chang JH, Shin JJ and Cho DH: Ursolic acid inhibits pigmentation by increasing melanosomal autophagy in B16F1 cells. Biochem Biophys Res Commun. 531:209–214. 2020. View Article : Google Scholar : PubMed/NCBI

29 

Arcamone F, Cassinelli G, Fantini G, Grein A, Orezzi P, Pol C and Spalla C: Adriamycin, 14-hydroxydaunomycin, a new antitumor antibiotic from S. peucetius var. caesius. Reprinted from biotechnology and bioengineering, Vol. XI, Issue 6, Pages 1101–1110 (1969). Biotechnol Bioeng. 67:704–713. 2000. View Article : Google Scholar : PubMed/NCBI

30 

Cortés-Funes H and Coronado C: Role of anthracyclines in the era of targeted therapy. Cardiovasc Toxicol. 7:56–60. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Weiss RB: The anthracyclines: Will we ever find a better doxorubicin? Semin Oncol. 19:670–686. 1992.PubMed/NCBI

32 

Sarmento-Ribeiro AB, Scorilas A, Goncalves AC, Efferth T and Trougakos IP: The emergence of drug resistance to targeted cancer therapies: Clinical evidence. Drug Resist Updat. 47:1006462019. View Article : Google Scholar : PubMed/NCBI

33 

Rui M, Xin Y, Li R, Ge Y, Feng C and Xu X: Targeted biomimetic nanoparticles for synergistic combination chemotherapy of paclitaxel and doxorubicin. Mol Pharm. 14:107–123. 2017. View Article : Google Scholar : PubMed/NCBI

34 

Fan YP, Liao JZ, Lu YQ, Tian DA, Ye F, Zhao PX, Xiang GY, Tang WX and He XX: MiR-375 and doxorubicin co-delivered by liposomes for combination therapy of hepatocellular carcinoma. Mol Ther Nucleic Acids. 7:181–189. 2017. View Article : Google Scholar : PubMed/NCBI

35 

Minotti G, Menna P, Salvatorelli E, Cairo G and Gianni L: Anthracyclines: Molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev. 56:185–229. 2004. View Article : Google Scholar : PubMed/NCBI

36 

Guo NF, Cao YJ, Chen X, Zhang Y, Fan YP, Liu J and Chen XL: Lixisenatide protects doxorubicin-induced renal fibrosis by activating wNF-κB/TNF-α and TGF-β/Smad pathways. Eur Rev Med Pharmacol Sci. 23:4017–4026. 2019.PubMed/NCBI

37 

Saleh D, Abdelbaset M, Hassan A, Sharaf O, Mahmoud S and Hegazy R: Omega-3 fatty acids ameliorate doxorubicin-induced cardiorenal toxicity: In-vivo regulation of oxidative stress, apoptosis and renal Nox4, and in-vitro preservation of the cytotoxic efficacy. PLoS One. 15:e02421752020. View Article : Google Scholar : PubMed/NCBI

38 

Prasanna PL, Renu K and Valsala Gopalakrishnan A: New molecular and biochemical insights of doxorubicin-induced hepatotoxicity. Life Sci. 250:1175992020. View Article : Google Scholar : PubMed/NCBI

39 

Zhou X, Xu P, Dang R, Guo Y, Li G, Qiao Y, Xie R, Liu Y and Jiang P: The involvement of autophagic flux in the development and recovery of doxorubicin-induced neurotoxicity. Free Radic Biol Med. 129:440–445. 2018. View Article : Google Scholar : PubMed/NCBI

40 

Yu FX, Zhao B and Guan KL: Hippo pathway in organ size control, tissue homeostasis, and cancer. Cell. 163:811–828. 2015. View Article : Google Scholar : PubMed/NCBI

41 

Kim CL, Choi SH and Mo JS: Role of the Hippo pathway in fibrosis and cancer. Cells. 8:4682019. View Article : Google Scholar : PubMed/NCBI

42 

Dong J, Feldmann G, Huang J, Wu S, Zhang N, Comerford SA, Gayyed MF, Anders RA, Maitra A and Pan D: Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell. 130:1120–1233. 2007. View Article : Google Scholar : PubMed/NCBI

43 

Avruch J, Zhou D and Bardeesy N: YAP oncogene overexpression supercharges colon cancer proliferation. Cell Cycle. 11:1090–1096. 2012. View Article : Google Scholar : PubMed/NCBI

44 

Liu XF, Han Q, Rong XZ, Yang M, Han YC, Yu JH and Lin XY: ANKHD1 promotes proliferation and invasion of non-small-cell lung cancer cells via regulating YAP oncoprotein expression and inactivating the Hippo pathway. Int J Oncol. 56:1175–1185. 2020.PubMed/NCBI

45 

Niu K, Liu Y, Zhou Z, Wu X, Wang H and Yan J: Antitumor effects of paeoniflorin on Hippo signaling pathway in gastric cancer cells. J Oncol. 2021:47249382021. View Article : Google Scholar : PubMed/NCBI

46 

Hou L, Chen L and Fang L: Scutellarin inhibits proliferation, invasion, and tumorigenicity in human breast cancer cells by regulating HIPPO-YAP signaling pathway. Med Sci Monit. 23:5130–5138. 2017. View Article : Google Scholar : PubMed/NCBI

47 

Driskill JH and Pan D: The Hippo pathway in liver homeostasis and pathophysiology. Annu Rev Pathol. 16:299–322. 2021. View Article : Google Scholar : PubMed/NCBI

48 

Masliantsev K, Karayan-Tapon L and Guichet PO: Hippo signaling pathway in gliomas. Cells. 10:1842021. View Article : Google Scholar : PubMed/NCBI

49 

Ansari D, Ohlsson H, Althini C, Bauden M, Zhou Q, Hu D and Andersson R: The Hippo signaling pathway in pancreatic cancer. Anticancer Res. 39:3317–3321. 2019. View Article : Google Scholar : PubMed/NCBI

50 

Llado V, Nakanishi Y, Duran A, Reina-Campos M, Shelton PM, Linares JF, Yajima T, Campos A, Aza-Blanc P, Leitges M, et al: Repression of intestinal stem cell function and tumorigenesis through direct phosphorylation of β-catenin and Yap by PKCζ. Cell Rep. 10:740–754. 2015. View Article : Google Scholar : PubMed/NCBI

51 

Chen L, Qin F, Deng X, Avruch J and Zhou D: Hippo pathway in intestinal homeostasis and tumorigenesis. Protein Cell. 3:305–310. 2012. View Article : Google Scholar : PubMed/NCBI

52 

Gu Y, Zhang L and Yu FX: Functions and regulations of the Hippo signaling pathway in intestinal homeostasis, regeneration and tumorigenesis. Yi Chuan. 39:588–596. 2017.PubMed/NCBI

53 

Zhou D, Zhang Y, Wu H, Barry E, Yin Y, Lawrence E, Dawson D, Willis JE, Markowitz SD, Camargo FD and Avruch J: Mst1 and Mst2 protein kinases restrain intestinal stem cell proliferation and colonic tumorigenesis by inhibition of Yes-associated protein (Yap) overabundance. Proc Natl Acad Sci USA. 108:E1312–E1320. 2011. View Article : Google Scholar : PubMed/NCBI

54 

Xiao Y, Liu Q, Peng N, Li Y, Qiu D, Yang T, Kang R, Usmani A, Amadasu E, Borlongan CV and Yu G: Lovastatin inhibits RhoA to suppress canonical Wnt/β-catenin signaling and alternative Wnt-YAP/TAZ signaling in colon cancer. Cell Transplant. 31:96368972210757492022. View Article : Google Scholar : PubMed/NCBI

55 

Touil Y, Igoudjil W, Corvaisier M, Dessein AF, Vandomme J, Monté D, Stechly L, Skrypek N, Langlois C, Grard G, et al: Colon cancer cells escape 5FU chemotherapy-induced cell death by entering stemness and quiescence associated with the c-Yes/YAP axis. Clin Cancer Res. 20:837–846. 2014. View Article : Google Scholar : PubMed/NCBI

56 

Shamekhi S, Abdolalizadeh J, Ostadrahimi A, Mohammadi SA, Barzegari A, Lotfi H, Bonabi E and Zarghami N: Apoptotic effect of saccharomyces cerevisiae on human colon cancer SW480 cells by regulation of Akt/NF-ĸB signaling pathway. Probiotics Antimicrob Proteins. 12:311–319. 2020. View Article : Google Scholar : PubMed/NCBI

57 

Goel S, Huang J and Klampfer L: K-Ras, intestinal homeostasis and colon cancer. Curr Clin Pharmacol. 10:73–81. 2015. View Article : Google Scholar : PubMed/NCBI

58 

Tumaneng K, Schlegelmilch K, Russell RC, Yimlamai D, Basnet H, Mahadevan N, Fitamant J, Bardeesy N, Camargo FD and Guan KL: YAP mediates crosstalk between the Hippo and PI(3)K-TOR pathways by suppressing PTEN via miR-29. Nat Cell Biol. 14:1322–1329. 2012. View Article : Google Scholar : PubMed/NCBI

59 

Yu FX, Zhao B, Panupinthu N, Jewell JL, Lian I, Wang LH, Zhao J, Yuan H, Tumaneng K, Li H, et al: Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell. 150:780–791. 2012. View Article : Google Scholar : PubMed/NCBI

60 

Kawai K, Viars C, Arden K, Tarin D, Urquidi V and Goodison S: Comprehensive karyotyping of the HT-29 colon adenocarcinoma cell line. Genes Chromosomes Cancer. 34:1–8. 2002. View Article : Google Scholar : PubMed/NCBI

61 

Grada A, Otero-Vinas M, Prieto-Castrillo F, Obagi Z and Falanga V: Research techniques made simple: Analysis of collective cell migration using the wound healing assay. J Invest Dermatol. 137:e11–e16. 2017. View Article : Google Scholar : PubMed/NCBI

62 

Vang Mouritzen M and Jenssen H: Optimized scratch assay for in vitro testing of cell migration with an automated optical camera. J Vis Exp. 576912018.PubMed/NCBI

63 

Martinotti S and Ranzato E: Scratch wound healing assay. Methods Mol Biol. 2109:225–229. 2020. View Article : Google Scholar : PubMed/NCBI

64 

Meng RY, Jin H, Nguyen TV, Chai OH, Park BH and Kim SM: Ursolic acid accelerates paclitaxel-induced cell death in esophageal cancer cells by suppressing Akt/FOXM1 signaling cascade. Int J Mol Sci. 22:114862021. View Article : Google Scholar : PubMed/NCBI

65 

Stephenson W: Deficiencies in the national institute of health's guidelines for the care and protection of laboratory animals. J Med Philos. 18:375–88. 1993. View Article : Google Scholar : PubMed/NCBI

66 

Kilkenny C, Browne WJ, Cuthill IC, Emerson M and Altman DG: Improving bioscience research reporting: The ARRIVE guidelines for reporting animal research. Osteoarthritis Cartilage. 20:256–260. 2012. View Article : Google Scholar : PubMed/NCBI

67 

Spangenberg EM and Keeling LJ: Assessing the welfare of laboratory mice in their home environment using animal-based measures-a benchmarking tool. Lab Anim. 50:30–38. 2016. View Article : Google Scholar : PubMed/NCBI

68 

Clayden EC: Practical section cutting and staining. 5th edition. Edinburgh: (15 Teviot Place, Edinburgh 1). Churchill Livingstone; 7. pp. pp2701971

69 

Kim DH, Kang DY, Sp N, Jo ES, Rugamba A, Jang KJ and Yang YM: Methylsulfonylmethane induces cell cycle arrest and apoptosis, and suppresses the stemness potential of HT-29 cells. Anticancer Res. 40:5191–5200. 2020. View Article : Google Scholar : PubMed/NCBI

70 

Ombrato L and Malanchi I: The EMT universe: Space between cancer cell dissemination and metastasis initiation. Crit Rev Oncog. 19:349–361. 2014. View Article : Google Scholar : PubMed/NCBI

71 

Wang C, Li Z, Lu Y, Du R, Katiyar S, Yang J, Fu M, Leader JE, Quong A, Novikoff PM and Pestell RG: Cyclin D1 repression of nuclear respiratory factor 1 integrates nuclear DNA synthesis and mitochondrial function. Proc Natl Acad Sci USA. 103:11567–11572. 2006. View Article : Google Scholar : PubMed/NCBI

72 

Bishnupuri KS, Alvarado DM, Khouri AN, Shabsovich M, Chen B, Dieckgraefe BK and Ciorba MA: IDO1 and kynurenine pathway metabolites activate PI3K-Akt signaling in the neoplastic colon epithelium to promote cancer cell proliferation and inhibit apoptosis. Cancer Res. 79:1138–1150. 2019. View Article : Google Scholar : PubMed/NCBI

73 

Ji J, Wang Z, Sun W, Li Z, Cai H, Zhao E and Cui H: Effects of cynaroside on cell proliferation, apoptosis, migration and invasion though the MET/AKT/mTOR axis in gastric cancer. Int J Mol Sci. 22:121252021. View Article : Google Scholar : PubMed/NCBI

74 

Zhang P, Yuan X, Yu T, Huang H, Yang C, Zhang L, Yang S, Luo X and Luo J: Lycorine inhibits cell proliferation, migration and invasion, and primarily exerts in vitro cytostatic effects in human colorectal cancer via activating the ROS/p38 and AKT signaling pathways. Oncol Rep. 45:192021. View Article : Google Scholar : PubMed/NCBI

75 

Yang L, Liu Y, Wang M, Qian Y, Dong X, Gu H, Wang H, Guo S and Hisamitsu T: Quercetin-induced apoptosis of HT-29 colon cancer cells via inhibition of the Akt-CSN6-Myc signaling axis. Mol Med Rep. 14:4559–4566. 2016. View Article : Google Scholar : PubMed/NCBI

76 

Guo C, Zhang X and Pfeifer GP: The tumor suppressor RASSF1A prevents dephosphorylation of the mammalian STE20-like kinases MST1 and MST2. J Biol Chem. 286:6253–6261. 2011. View Article : Google Scholar : PubMed/NCBI

77 

Kim M, Kim M, Lee MS, Kim CH and Lim DS: The MST1/2-SAV1 complex of the Hippo pathway promotes ciliogenesis. Nat Commun. 5:53702014. View Article : Google Scholar : PubMed/NCBI

78 

Shome D, von Woedtke T, Riedel K and Masur K: The HIPPO transducer YAP and its targets CTGF and Cyr61 drive a paracrine signalling in cold atmospheric plasma-mediated wound healing. Oxid Med Cell Longev. 2020:49102802020. View Article : Google Scholar : PubMed/NCBI

79 

Wang Y, Kuramitsu Y, Baron B, Kitagawa T, Tokuda K, Akada J, Maehara SI, Maehara Y and Nakamura K: PI3K inhibitor LY294002, as opposed to wortmannin, enhances AKT phosphorylation in gemcitabine-resistant pancreatic cancer cells. Int J Oncol. 50:606–612. 2017. View Article : Google Scholar : PubMed/NCBI

80 

Lin J, Chen Y, Wei L, Hong Z, Sferra TJ and Peng J: Ursolic acid inhibits colorectal cancer angiogenesis through suppression of multiple signaling pathways. Int J Oncol. 43:1666–1674. 2013. View Article : Google Scholar : PubMed/NCBI

81 

Zhang Y, Huang L, Shi H, Chen H, Tao J, Shen R and Wang T: Ursolic acid enhances the therapeutic effects of oxaliplatin in colorectal cancer by inhibition of drug resistance. Cancer Sci. 109:94–102. 2018. View Article : Google Scholar : PubMed/NCBI

82 

Zeng Q, Che Y, Zhang Y, Chen M, Guo Q and Zhang W: Thymol isolated from thymus vulgaris L. inhibits colorectal cancer cell growth and metastasis by suppressing the Wnt/β-catenin pathway. Drug Des Devel Ther. 14:2535–2547. 2020. View Article : Google Scholar : PubMed/NCBI

83 

Yao M, Ma X, Zhang X, Shi L, Liu T, Liang X, Zhao H, Li X, Li L, Gao H, et al: Lectin-mediated pH-sensitive doxorubicin prodrug for pre-targeted chemotherapy of colorectal cancer with enhanced efficacy and reduced side effects. Theranostics. 9:747–760. 2019. View Article : Google Scholar : PubMed/NCBI

84 

O'Bryan RM, Baker LH, Gottlieb JE, Rivkin SE, Balcerzak SP, Grumet GN, Salmon SE, Moon TE and Hoogstraten B: Dose response evaluation of adriamycin in human neoplasia. Cancer. 39:1940–1948. 1977. View Article : Google Scholar : PubMed/NCBI

85 

Gabizon A, Shmeeda H and Barenholz Y: Pharmacokinetics of pegylated liposomal doxorubicin: Review of animal and human studies. Clin Pharmacokinet. 42:419–436. 2003. View Article : Google Scholar : PubMed/NCBI

86 

Marina NM, Cochrane D, Harney E, Zomorodi K, Blaney S, Winick N, Bernstein M and Link MP: Dose escalation and pharmacokinetics of pegylated liposomal doxorubicin (Doxil) in children with solid tumors: A pediatric oncology group study. Clin Cancer Res. 8:413–418. 2002.PubMed/NCBI

87 

Nair AB and Jacob S: A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm. 7:27–31. 2016. View Article : Google Scholar : PubMed/NCBI

88 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2019. CA Cancer J Clin. 69:7–34. 2019. View Article : Google Scholar : PubMed/NCBI

89 

Xie YH, Chen YX and Fang JY: Comprehensive review of targeted therapy for colorectal cancer. Signal Transduct Target Ther. 5:222020. View Article : Google Scholar : PubMed/NCBI

90 

Li J, Ma X, Chakravarti D, Shalapour S and DePinho RA: Genetic and biological hallmarks of colorectal cancer. Genes Dev. 35:787–820. 2021. View Article : Google Scholar : PubMed/NCBI

91 

Tiwari A, Saraf S, Verma A, Panda PK and Jain SK: Novel targeting approaches and signaling pathways of colorectal cancer: An insight. World J Gastroenterol. 24:4428–4435. 2018. View Article : Google Scholar : PubMed/NCBI

92 

Krishnamurthy N and Kurzrock R: Targeting the Wnt/beta-catenin pathway in cancer: Update on effectors and inhibitors. Cancer Treat Rev. 62:50–60. 2018. View Article : Google Scholar : PubMed/NCBI

93 

Chen Z, Oh D, Dubey AK, Yao M, Yang B, Groves JT and Sheetz M: EGFR family and Src family kinase interactions: Mechanics matters? Curr Opin Cell Biol. 51:97–102. 2018. View Article : Google Scholar : PubMed/NCBI

94 

Lopez A, Harada K, Vasilakopoulou M, Shanbhag N and Ajani JA: Targeting angiogenesis in colorectal carcinoma. Drugs. 79:63–74. 2019. View Article : Google Scholar : PubMed/NCBI

95 

Ahmad R, Singh JK, Wunnava A, Al-Obeed O, Abdulla M and Srivastava SK: Emerging trends in colorectal cancer: Dysregulated signaling pathways (Review). Int J Mol Med. 47:142021. View Article : Google Scholar : PubMed/NCBI

96 

Kassi E, Sourlingas TG, Spiliotaki M, Papoutsi Z, Pratsinis H, Aligiannis N and Moutsatsou P: Ursolic acid triggers apoptosis and Bcl-2 downregulation in MCF-7 breast cancer cells. Cancer Invest. 27:723–733. 2009. View Article : Google Scholar : PubMed/NCBI

97 

Yim EK, Lee KH, Namkoong SE, Um SJ and Park JS: Proteomic analysis of ursolic acid-induced apoptosis in cervical carcinoma cells. Cancer Lett. 235:209–220. 2006. View Article : Google Scholar : PubMed/NCBI

98 

Argenziano M, Gigliotti CL, Clemente N, Boggio E, Ferrara B, Trotta F, Pizzimenti S, Barrera G, Boldorini R, Bessone F, et al: Improvement in the anti-tumor efficacy of doxorubicin nanosponges in in vitro and in mice bearing breast tumor models. Cancers (Basel). 12:1622020. View Article : Google Scholar : PubMed/NCBI

99 

Brattain MG, Brattain DE, Fine WD, Khaled FM, Marks ME, Kimball PM, Arcolano LA and Danbury BH: Initiation and characterization of cultures of human colonic carcinoma with different biological characteristics utilizing feeder layers of confluent fibroblasts. Oncodev Biol Med. 2:355–366. 1981.PubMed/NCBI

100 

Brattain MG, Fine WD, Khaled FM, Thompson J and Brattain DE: Heterogeneity of malignant cells from a human colonic carcinoma. Cancer Res. 41:1751–1756. 1981.PubMed/NCBI

101 

Ahmed D, Eide PW, Eilertsen IA, Danielsen SA, Eknaes M, Hektoen M, Lind GE and Lothe RA: Epigenetic and genetic features of 24 colon cancer cell lines. Oncogenesis. 2:e712013. View Article : Google Scholar : PubMed/NCBI

102 

Bazan V, Migliavacca M, Zanna I, Tubiolo C, Grassi N, Latteri MA, La Farina M, Albanese I, Dardanoni G, Salerno S, et al: Specific codon 13 K-ras mutations are predictive of clinical outcome in colorectal cancer patients, whereas codon 12 K-ras mutations are associated with mucinous histotype. Ann Oncol. 13:1438–1446. 2002. View Article : Google Scholar : PubMed/NCBI

103 

Lupertz R, Watjen W, Kahl R and Chovolou Y: Dose- and time-dependent effects of doxorubicin on cytotoxicity, cell cycle and apoptotic cell death in human colon cancer cells. Toxicology. 271:115–121. 2010. View Article : Google Scholar : PubMed/NCBI

104 

Nie W, Zan X, Yu T, Ran M, Hong Z, He Y, Yang T, Ju Y and Gao X: Synergetic therapy of glioma mediated by a dual delivery system loading α-mangostin and doxorubicin through cell cycle arrest and apoptotic pathways. Cell Death Dis. 11:9282020. View Article : Google Scholar : PubMed/NCBI

105 

Tilija Pun N, Jang WJ and Jeong CH: Role of autophagy in regulation of cancer cell death/apoptosis during anti-cancer therapy: Focus on autophagy flux blockade. Arch Pharm Res. 43:475–488. 2020. View Article : Google Scholar : PubMed/NCBI

106 

Lin YJ, Liang WM, Chen CJ, Tsang H, Chiou JS, Liu X, Cheng CF, Lin TH, Liao CC, Huang SM, et al: Network analysis and mechanisms of action of Chinese herb-related natural compounds in lung cancer cells. Phytomedicine. 58:1528932019. View Article : Google Scholar : PubMed/NCBI

107 

Doğan Şiğva ZÖ, Balci Okcanoğlu T, Biray Avci Ç, Yilmaz Süslüer S, Kayabaşi Ç, Turna B, Dodurga Y, Nazli O and Gündüz C: Investigation of the synergistic effects of paclitaxel and herbal substances and endemic plant extracts on cell cycle and apoptosis signal pathways in prostate cancer cell lines. Gene. 687:261–271. 2019. View Article : Google Scholar : PubMed/NCBI

108 

Aiello P, Sharghi M, Mansourkhani SM, Ardekan AP, Jouybari L, Daraei N, Peiro K, Mohamadian S, Rezaei M, Heidari M, et al: Medicinal plants in the prevention and treatment of colon cancer. Oxid Med Cell Longev. 2019:20756142019. View Article : Google Scholar : PubMed/NCBI

109 

Phan T, Nguyen VH, A'Lincourt Salazar M, Wong P, Diamond DJ, Yim JH and Melstrom LG: Inhibition of autophagy amplifies baicalein-induced apoptosis in human colorectal cancer. Mol Ther Oncolytics. 19:1–7. 2020. View Article : Google Scholar : PubMed/NCBI

110 

Mandal S, Gamit N, Varier L, Dharmarajan A and Warrier S: Inhibition of breast cancer stem-like cells by a triterpenoid, ursolic acid, via activation of Wnt antagonist, sFRP4 and suppression of miRNA-499a-5p. Life Sci. 265:1188542021. View Article : Google Scholar : PubMed/NCBI

111 

Zheng JL, Wang SS, Shen KP, Chen L, Peng X, Chen JF, An HM and Hu B: Ursolic acid induces apoptosis and anoikis in colorectal carcinoma RKO cells. BMC Complement Med Ther. 21:522021. View Article : Google Scholar : PubMed/NCBI

112 

Yang S, Zhang X, Qu H, Qu B, Yin X and Zhao H: Cabozantinib induces PUMA-dependent apoptosis in colon cancer cells via AKT/GSK-3β/NF-κB signaling pathway. Cancer Gene Ther. 27:368–377. 2020. View Article : Google Scholar : PubMed/NCBI

113 

Qin J, Fu M, Wang J, Huang F, Liu H, Huangfu M, Yu D, Liu H, Li X, Guan X and Chen X: PTEN/AKT/mTOR signaling mediates anticancer effects of epigallocatechin-3-gallate in ovarian cancer. Oncol Rep. 43:1885–1896. 2020.PubMed/NCBI

114 

Zhu ML, Zhang PM, Jiang M, Yu SW and Wang L: Myricetin induces apoptosis and autophagy by inhibiting PI3K/Akt/mTOR signalling in human colon cancer cells. BMC Complement Med Ther. 20:2092020. View Article : Google Scholar : PubMed/NCBI

115 

Li W, Li C, Ma L and Jin F: Resveratrol inhibits viability and induces apoptosis in the small-cell lung cancer H446 cell line via the PI3K/Akt/c-Myc pathway. Oncol Rep. 44:1821–1830. 2020.PubMed/NCBI

116 

Tian J, Zhang H, Mu L, Wang M, Li X, Zhang X, Xie E, Ma M, Wu D and Du Y: The miR-218/GAB2 axis regulates proliferation, invasion and EMT via the PI3K/AKT/GSK-3β pathway in prostate cancer. Exp Cell Res. 394:1121282020. View Article : Google Scholar : PubMed/NCBI

117 

Qi X, Sun L, Wan J, Xu R, He S and Zhu X: Tensin4 promotes invasion and migration of gastric cancer cells via regulating AKT/GSK-3β/snail signaling pathway. Pathol Res Pract. 216:1530012020. View Article : Google Scholar : PubMed/NCBI

118 

Chang YX, Lin YF, Chen CL, Huang MS, Hsiao M and Liang PH: Chaperonin-containing TCP-1 promotes cancer chemoresistance and metastasis through the AKT-GSK3β-β-catenin and XIAP-survivin pathways. Cancers (Basel). 12:38652020. View Article : Google Scholar : PubMed/NCBI

119 

Ding L, Cao J, Lin W, Chen H, Xiong X, Ao H, Yu M, Lin J and Cui Q: The roles of cyclin-dependent kinases in cell-cycle progression and therapeutic strategies in human breast cancer. Int J Mol Sci. 21:19602020. View Article : Google Scholar : PubMed/NCBI

120 

Xu S, Zhang H, Liu T, Yang W, Lv W, He D, Guo P and Li L: 6-Gingerol induces cell-cycle G1-phase arrest through AKT-GSK 3β-cyclin D1 pathway in renal-cell carcinoma. Cancer Chemother Pharmacol. 85:379–390. 2020. View Article : Google Scholar : PubMed/NCBI

121 

Zhou C, Du J, Zhao L, Liu W, Zhao T, Liang H, Fang P, Zhang K and Zeng H: GLI1 reduces drug sensitivity by regulating cell cycle through PI3K/AKT/GSK3/CDK pathway in acute myeloid leukemia. Cell Death Dis. 12:2312021. View Article : Google Scholar : PubMed/NCBI

122 

Zhang S, Liu X, Bawa-Khalfe T, Lu LS, Lyu YL, Liu LF and Yeh ET: Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med. 18:1639–1642. 2012. View Article : Google Scholar : PubMed/NCBI

123 

Desai VG, Lee T, Moland CL, Vijay V, Han T, Lewis SM, Herman EH and Fuscoe JC: Candidate early predictive plasma protein markers of doxorubicin-induced chronic cardiotoxicity in B6C3F1 mice. Toxicol Appl Pharmacol. 363:164–173. 2019. View Article : Google Scholar : PubMed/NCBI

124 

Kuenzi BM and Ideker T: Author correction: A census of pathway maps in cancer systems biology. Nat Rev Cancer. 21:2122021. View Article : Google Scholar : PubMed/NCBI

125 

Kuenzi BM and Ideker T: A census of pathway maps in cancer systems biology. Nat Rev Cancer. 20:233–246. 2020. View Article : Google Scholar : PubMed/NCBI

126 

Chang YC, Wu JW, Wang CW and Jang AC: Hippo signaling-mediated mechanotransduction in cell movement and cancer metastasis. Front Mol Biosci. 6:1572020. View Article : Google Scholar : PubMed/NCBI

127 

Kennedy MB: Origin of PDZ (DHR, GLGF) domains. Trends Biochem Sci. 20:3501995. View Article : Google Scholar : PubMed/NCBI

128 

Zheng Y and Pan D: The Hippo signaling pathway in development and disease. Dev Cell. 50:264–282. 2019. View Article : Google Scholar : PubMed/NCBI

129 

Furth N and Aylon Y: The LATS1 and LATS2 tumor suppressors: Beyond the Hippo pathway. Cell Death Differ. 24:1488–1501. 2017. View Article : Google Scholar : PubMed/NCBI

130 

Kim SH, Jin H, Meng RY, Kim DY, Liu YC, Chai OH, Park BH and Kim SM: Activating Hippo pathway via Rassf1 by ursolic acid suppresses the tumorigenesis of gastric cancer. Int J Mol Sci. 20:47092019. View Article : Google Scholar : PubMed/NCBI

131 

Jeong SH, Kim HB, Kim MC, Lee JM, Lee JH, Kim JH, Kim JW, Park WY, Kim SY, Kim JB, et al: Hippo-mediated suppression of IRS2/AKT signaling prevents hepatic steatosis and liver cancer. J Clin Invest. 128:1010–1025. 2018. View Article : Google Scholar : PubMed/NCBI

132 

Zhang S, Chen Q, Liu Q, Li Y, Sun X, Hong L, Ji S, Liu C, Geng J, Zhang W, et al: Hippo signaling suppresses cell ploidy and tumorigenesis through Skp2. Cancer Cell. 31:669–684.e7. 2017. View Article : Google Scholar : PubMed/NCBI

133 

Ahmed AA, Abedalthagafi M, Anwar AE and Bui MM: Akt and Hippo pathways in Ewing's sarcoma tumors and their prognostic significance. J Cancer. 6:1005–1010. 2015. View Article : Google Scholar : PubMed/NCBI

134 

Berthold R, Isfort I, Erkut C, Heinst L, Grunewald I, Wardelmann E, Kindler T, Åman P, Grünewald TGP, Cidre-Aranaz F, et al: Fusion protein-driven IGF-IR/PI3K/AKT signals deregulate Hippo pathway promoting oncogenic cooperation of YAP1 and FUS-DDIT3 in myxoid liposarcoma. Oncogenesis. 11:202022. View Article : Google Scholar : PubMed/NCBI

135 

Ma W, Han C, Zhang J, Song K, Chen W, Kwon H and Wu T: The histone methyltransferase G9a promotes cholangiocarcinogenesis through regulation of the Hippo pathway kinase LATS2 and YAP signaling pathway. Hepatology. 72:1283–1297. 2020. View Article : Google Scholar : PubMed/NCBI

136 

Xu W, Yang Z, Xie C, Zhu Y, Shu X, Zhang Z, Li N, Chai N, Zhang S, Wu K, et al: PTEN lipid phosphatase inactivation links the hippo and PI3K/Akt pathways to induce gastric tumorigenesis. J Exp Clin Cancer Res. 37:1982018. View Article : Google Scholar : PubMed/NCBI

137 

Jang SW, Yang SJ, Srinivasan S and Ye K: Akt phosphorylates MstI and prevents its proteolytic activation, blocking FOXO3 phosphorylation and nuclear translocation. J Biol Chem. 282:30836–30844. 2007. View Article : Google Scholar : PubMed/NCBI

138 

Romano D, Matallanas D, Weitsman G, Preisinger C, Ng T and Kolch W: Proapoptotic kinase MST2 coordinates signaling crosstalk between RASSF1A, Raf-1, and Akt. Cancer Res. 70:1195–1203. 2010. View Article : Google Scholar : PubMed/NCBI

139 

Kim D, Shu S, Coppola MD, Kaneko S, Yuan ZQ and Cheng JQ: Regulation of proapoptotic mammalian ste20-like kinase MST2 by the IGF1-Akt pathway. PLoS One. 5:e96162010. View Article : Google Scholar : PubMed/NCBI

140 

Kim SM, Ye S, Rah SY, Park BH, Wang H, Kim JR, Kim SH, Jang KY and Lee KB: RhBMP-2 activates Hippo signaling through RASSF1 in esophageal cancer cells. Sci Rep. 6:268212016. View Article : Google Scholar : PubMed/NCBI

141 

Pankova D, Jiang Y, Chatzifrangkeskou M, Vendrell I, Buzzelli J, Ryan A, Brown C and O'Neill E: RASSF1A controls tissue stiffness and cancer stem-like cells in lung adenocarcinoma. EMBO J. 38:e1005322019. View Article : Google Scholar : PubMed/NCBI

142 

Gupta V, Agarwal P and Deshpande P: Impact of RASSF1A gene methylation on clinico-pathological features of tumor and non-tumor tissue of breast cancer. Ann Diagn Pathol. 52:1517222021. View Article : Google Scholar : PubMed/NCBI

143 

Lee NH, Kim SJ and Hyun J: MicroRNAs regulating Hippo-YAP signaling in liver cancer. Biomedicines. 9:3472021. View Article : Google Scholar : PubMed/NCBI

144 

Agarwal S, Amin KS, Jagadeesh S, Baishay G, Rao PG, Barua NC, Bhattacharya S and Banerjee PP: Mahanine restores RASSF1A expression by down-regulating DNMT1 and DNMT3B in prostate cancer cells. Mol Cancer. 12:992013. View Article : Google Scholar : PubMed/NCBI

145 

Blanchard TG, Lapidus R, Banerjee V, Bafford AC, Czinn SJ, Ahmed H and Banerjee A: Upregulation of RASSF1A in colon cancer by suppression of angiogenesis signaling and Akt activation. Cell Physiol Biochem. 48:1259–1273. 2018. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Hu D, Meng RY, Nguyen TV, Chai OH, Park BH, Lee J and Kim SM: Inhibition of colorectal cancer tumorigenesis by ursolic acid and doxorubicin is mediated by targeting the Akt signaling pathway and activating the Hippo signaling pathway. Mol Med Rep 27: 11, 2023.
APA
Hu, D., Meng, R.Y., Nguyen, T.V., Chai, O.H., Park, B.H., Lee, J., & Kim, S.M. (2023). Inhibition of colorectal cancer tumorigenesis by ursolic acid and doxorubicin is mediated by targeting the Akt signaling pathway and activating the Hippo signaling pathway. Molecular Medicine Reports, 27, 11. https://doi.org/10.3892/mmr.2022.12898
MLA
Hu, D., Meng, R. Y., Nguyen, T. V., Chai, O. H., Park, B. H., Lee, J., Kim, S. M."Inhibition of colorectal cancer tumorigenesis by ursolic acid and doxorubicin is mediated by targeting the Akt signaling pathway and activating the Hippo signaling pathway". Molecular Medicine Reports 27.1 (2023): 11.
Chicago
Hu, D., Meng, R. Y., Nguyen, T. V., Chai, O. H., Park, B. H., Lee, J., Kim, S. M."Inhibition of colorectal cancer tumorigenesis by ursolic acid and doxorubicin is mediated by targeting the Akt signaling pathway and activating the Hippo signaling pathway". Molecular Medicine Reports 27, no. 1 (2023): 11. https://doi.org/10.3892/mmr.2022.12898
Copy and paste a formatted citation
x
Spandidos Publications style
Hu D, Meng RY, Nguyen TV, Chai OH, Park BH, Lee J and Kim SM: Inhibition of colorectal cancer tumorigenesis by ursolic acid and doxorubicin is mediated by targeting the Akt signaling pathway and activating the Hippo signaling pathway. Mol Med Rep 27: 11, 2023.
APA
Hu, D., Meng, R.Y., Nguyen, T.V., Chai, O.H., Park, B.H., Lee, J., & Kim, S.M. (2023). Inhibition of colorectal cancer tumorigenesis by ursolic acid and doxorubicin is mediated by targeting the Akt signaling pathway and activating the Hippo signaling pathway. Molecular Medicine Reports, 27, 11. https://doi.org/10.3892/mmr.2022.12898
MLA
Hu, D., Meng, R. Y., Nguyen, T. V., Chai, O. H., Park, B. H., Lee, J., Kim, S. M."Inhibition of colorectal cancer tumorigenesis by ursolic acid and doxorubicin is mediated by targeting the Akt signaling pathway and activating the Hippo signaling pathway". Molecular Medicine Reports 27.1 (2023): 11.
Chicago
Hu, D., Meng, R. Y., Nguyen, T. V., Chai, O. H., Park, B. H., Lee, J., Kim, S. M."Inhibition of colorectal cancer tumorigenesis by ursolic acid and doxorubicin is mediated by targeting the Akt signaling pathway and activating the Hippo signaling pathway". Molecular Medicine Reports 27, no. 1 (2023): 11. https://doi.org/10.3892/mmr.2022.12898
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team