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
June-2018 Volume 17 Issue 6

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
June-2018 Volume 17 Issue 6

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
Article Open Access

Synergistic anticancer effects of bufalin and sorafenib by regulating apoptosis associated proteins

  • Authors:
    • Haiyong Wang
    • Chenyue Zhang
    • Huiying Chi
    • Zhiqiang Meng
  • View Affiliations / Copyright

    Affiliations: Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China, Shanghai Geriatrics Institute of Traditional Chinese Medicine, Shanghai 200032, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 8101-8110
    |
    Published online on: April 24, 2018
       https://doi.org/10.3892/mmr.2018.8927
  • 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

As one of the most recognized and well‑known drugs for hepatocellular carcinoma (HCC), the antitumor effect of sorafenib against HCC remains to be improved. Bufalin has displayed an antitumor effect in HCC; however, whether the enhanced antitumor effect may be generated with their combined treatment remains unclear. Therefore, in the present study, their combined effects on HCC proliferation and apoptosis were investigated. It was revealed that either bufalin or sorafenib suppressed PLC/PRF/5 and SMMC‑7721 cell proliferation in a concentration‑dependent manner following incubation for 24 h, and the inhibitory effect was augmented with their combined treatment. The synergistic effect peaked in HCC cells treated with 20 nM bufalin and 10 µM sorafenib. In addition, cell cycle and terminal deoxynucleotidyl transferase dUTP nick‑end labelling assays revealed that bufalin also enhanced sorafenib‑induced apoptosis. Colony formation assay demonstrated that combined treatment significantly suppressed HCC proliferation compared with treatment with either of them alone. Furthermore, B‑cell lymphoma 2‑associated X protein, caspase 7 and poly‑(adenosine diphosphate‑ribose) polymerase were upregulated in HCC cells with combined treatment. Taken together, the results of the present study revealed that the treatment of sorafenib combined with bufalin synergistically suppressed HCC proliferation and induced apoptosis. Therefore, bufalin combined with sorafenib may be a favorable treatment strategy for patients with HCC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Llovet JM, Burroughs A and Bruix J: Hepatocellular carcinoma. Lancet. 362:1907–1917. 2003. View Article : Google Scholar : PubMed/NCBI

2 

Bosch FX, Ribes J, Diaz M and Cleries R: Primary livercancer: Worldwide incidence and trends. Gastroenterology. 127 5 Suppl 1:S5–S16. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, Chen C, Zhang X, Vincent P, McHugh M, et al: BAY 43–9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 64:7099–7109. 2004. View Article : Google Scholar : PubMed/NCBI

4 

Carlomagno F, Anaganti S, Guida T, Salvatore G, Troncone G, Wilhelm SM and Santoro M: BAY 43–9006 inhibition of oncogenic RET mutants. J Natl Cancer Inst. 98:326–334. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Chang YS, Adnane J, Trail PA, Levy J, Henderson A, Xue D, Bortolon E, Ichetovkin M, Chen C, McNabola A, et al: Sorafenib (BAY 43–9006) inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models. Cancer Chemother Pharmacol. 59:561–574. 2007. View Article : Google Scholar : PubMed/NCBI

6 

Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, et al: SHARP investigators study group: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 359:378–390. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Qi F, Li A, Inagaki Y, Kokudo N, Tamura S, Nakata M and Tang W: Antitumor activity of extracts and compounds from the skin of the toad Bufo bufo gargarizans Cantor. Int Immunopharmacol. 11:342–349. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Takai N, Ueda T, Nishida M, Nasu K and Narahara H: Bufalin induces growth inhibition, cell cycle arrest and apoptosis in human endometrial and ovarian cancer cells. Int J Mol Med. 21:637–643. 2008.PubMed/NCBI

9 

Huang WW, Yang JS, Pai SJ, Wu PP, Chang SJ, Chueh FS, Fan MJ, Chiou SM, Kuo HM, Yeh CC, et al: Bufalin induces G0/G1 phase arrest through inhibiting the levels of cyclin D, cyclin E, CDK2 and CDK4 and triggers apoptosis via mitochondrial signaling pathway in T24 human bladder cancer cells. Mutat Res. 732:26–33. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Yin JQ, Shen JN, Su WW, Wang J, Huang G, Jin S, Guo QC, Zou CY, Li HM and Li FB: Bufalin induces apoptosis in human osteosarcoma U-2OS and U-2OS methotrexate300-resistant cell lines. Acta Pharmacol Sin. 28:712–720. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Efferth T, Davey M, Olbrich A, Rücker G, Gebhart E and Davey R: Activity of drugs from traditional Chinese medicine toward sensitive and MDR1- or MRP1-overexpressing multidrug-resistant human CCRF-CEM leukemia cells. Blood Cells Mol Dis. 28:160–168. 2002. View Article : Google Scholar : PubMed/NCBI

12 

Wang H, Zhang C, Ning Z, Xu L, Zhu X and Meng Z: Bufalin enhances anti-angiogenic effect of sorafenib via AKT/VEGF signaling. Int J Oncol. 48:1229–1241. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Wang H, Zhang C, Xu L, Zang K, Ning Z, Jiang F, Chi H, Zhu X and Meng Z: Bufalin suppresses hepatocellular carcinoma invasion and metastasis by targeting HIF-1α via the PI3K/AKT/mTOR pathway. Oncotarget. 7:20193–20208. 2016.PubMed/NCBI

14 

Chen S, Wang G, Niu X, Zhao J, Tan W, Wang H, Zhao L and Ge Y: Combination of AZD2281 (Olaparib) and GX15-070 (Obatoclax) results in synergistic antitumor activities in preclinical models of pancreatic cancer. Cancer Lett. 348:20–28. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Liu J, Cui X, Qu L, Hua L, Wu M, Shen Z, Lu C and Ni R: Overexpression of DLX2 is associated with poor prognosis and sorafenib resistance in hepatocellular carcinoma. Exp Mol Pathol. 101:58–65. 2016. View Article : Google Scholar : PubMed/NCBI

16 

Wang J, Chen C, Wang S, Zhang Y, Yin P, Gao Z, Xu J, Feng D, Zuo Q, Zhao R and Chen T: Bufalin inhibits HCT116 colon cancer cells and its orthotopic xenograft tumor in mice model through genes related to apoptotic and PTEN/AKT pathways. Gastroenterol Res Pract. 2015:4571932015. View Article : Google Scholar : PubMed/NCBI

17 

Zhai B, Hu F, Yan H, Zhao D, Jin X, Fang T, Pan S, Sun X and Xu L: Bufalin reverses resistance to sorafenib by inhibiting Akt activation in hepatocellular carcinoma: The role of endoplasmic reticulum stress. PLoS One. 10:e01384852015. View Article : Google Scholar : PubMed/NCBI

18 

Hajra KM and Liu JR: Apoptosome dysfunction in human cancer. Apoptosis. 9:691–704. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Ghavami S, Hashemi M, Ande SR, Yeganeh B, Xiao W, Eshraghi M, Bus CJ, Kadkhoda K, Wiechec E, Halayko AJ, et al: Apoptosis and cancer: Mutations within caspase genes. J Med Genet. 46:497–510. 2009. View Article : Google Scholar : PubMed/NCBI

20 

He GW, Günther C, Thonn V, Yu YQ, Martini E, Buchen B, Neurath MF, Stürzl M and Becker C: Regression of apoptosis-resistant colorectal tumors by induction of necroptosis in mice. J Exp Med. 214:1655–1662. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Ucker DS and Levine JS: Exploitation of apoptotic regulation in cancer. Front Immunol. 9:2412018. View Article : Google Scholar : PubMed/NCBI

22 

Green DR: Apoptotic pathways: Ten min to dead. Cell. 121:671–674. 2005. View Article : Google Scholar : PubMed/NCBI

23 

Ouyang L, Shi Z, Zhao S, Wang FT, Zhou TT, Liu B and Bao JK: Programmed cell death pathways in cancer: A review of apoptosis, autophagy and programmed necrosis. Cell Prolif. 45:487–498. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Kwon KB, Park BH and Ryu DG: Chemotherapy through mitochondrial apoptosis using nutritional supplements and herbs: A brief overview. J Bioenerg Biomembr. 39:31–34. 2007. View Article : Google Scholar : PubMed/NCBI

25 

Shi YH, Ding ZB, Zhou J, Hui B, Shi GM, Ke AW, Wang XY, Dai Z, Peng YF, Gu CY, et al: Targeting autophagy enhances sorafenib lethality for hepatocellular carcinoma via ER stress-related apoptosis. Autophagy. 7:1159–1172. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Liu L, Cao Y, Chen C, Zhang X, McNabola A, Wilkie D, Wilhelm S, Lynch M and Carter C: Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res. 66:11851–11858. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Fadeel B and Orrenius S: Apoptosis: A basic biological phenomenon with wide-ranging implications in human disease. J Intern Med. 258:479–517. 2005. View Article : Google Scholar : PubMed/NCBI

28 

Ly JD, Grubb DR and Lawen A: The mitochondrial membrane potential (deltapsi (m)) in apoptosis; an update. Apoptosis. 8:115–128. 2003. View Article : Google Scholar : PubMed/NCBI

29 

Ji BC, Hsu WH, Yang JS, Hsia TC, Lu CC, Chiang JH, Yang JL, Lin CH, Lin JJ, Suen LJ, et al: Gallic acid induces apoptosis via caspase-3 and mitochondrion-dependent pathways in vitro and suppresses lung xenograft tumor growth in vivo. J Agric Food Chem. 57:7596–7604. 2009. View Article : Google Scholar : PubMed/NCBI

30 

Logue SE and Martin SJ: Caspase activation cascades in apoptosis. Biochem Soc Trans. 36:1–9. 2008. View Article : Google Scholar : PubMed/NCBI

31 

Tang Z, Takahashi Y, Chen C, Liu Y, He H, Tsotakos N, Serfass JM, Gebru MT, Chen H, Young MM and Wang HG: Atg2A/B deficiency switches cytoprotective autophagy to non-canonical caspase-8 activation and apoptosis. Cell Death Differ. 24:2127–2138. 2017. View Article : Google Scholar : PubMed/NCBI

32 

Concha NO and Abdel-Meguid SS: Controlling apoptosis by inhibition of caspases. Curr Med Chem. 9:713–726. 2002. View Article : Google Scholar : PubMed/NCBI

33 

Martinou JC and Youle RJ: Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics. Dev Cell. 21:92–101. 2011. View Article : Google Scholar : PubMed/NCBI

34 

Adams JM and Cory S: The Bcl-2 protein family: Arbiters of cell survival. Science. 281:1322–1326. 1998. View Article : Google Scholar : PubMed/NCBI

35 

Zheng Q, Wang B, Gao J, Xin N, Wang W, Song X, Shao Y and Zhao C: CD155 knockdown promotes apoptosis via AKT/Bcl-2/Bax in colon cancer cells. J Cell Mol Med. 22:131–140. 2018. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang H, Zhang C, Chi H and Meng Z: Synergistic anticancer effects of bufalin and sorafenib by regulating apoptosis associated proteins. Mol Med Rep 17: 8101-8110, 2018.
APA
Wang, H., Zhang, C., Chi, H., & Meng, Z. (2018). Synergistic anticancer effects of bufalin and sorafenib by regulating apoptosis associated proteins. Molecular Medicine Reports, 17, 8101-8110. https://doi.org/10.3892/mmr.2018.8927
MLA
Wang, H., Zhang, C., Chi, H., Meng, Z."Synergistic anticancer effects of bufalin and sorafenib by regulating apoptosis associated proteins". Molecular Medicine Reports 17.6 (2018): 8101-8110.
Chicago
Wang, H., Zhang, C., Chi, H., Meng, Z."Synergistic anticancer effects of bufalin and sorafenib by regulating apoptosis associated proteins". Molecular Medicine Reports 17, no. 6 (2018): 8101-8110. https://doi.org/10.3892/mmr.2018.8927
Copy and paste a formatted citation
x
Spandidos Publications style
Wang H, Zhang C, Chi H and Meng Z: Synergistic anticancer effects of bufalin and sorafenib by regulating apoptosis associated proteins. Mol Med Rep 17: 8101-8110, 2018.
APA
Wang, H., Zhang, C., Chi, H., & Meng, Z. (2018). Synergistic anticancer effects of bufalin and sorafenib by regulating apoptosis associated proteins. Molecular Medicine Reports, 17, 8101-8110. https://doi.org/10.3892/mmr.2018.8927
MLA
Wang, H., Zhang, C., Chi, H., Meng, Z."Synergistic anticancer effects of bufalin and sorafenib by regulating apoptosis associated proteins". Molecular Medicine Reports 17.6 (2018): 8101-8110.
Chicago
Wang, H., Zhang, C., Chi, H., Meng, Z."Synergistic anticancer effects of bufalin and sorafenib by regulating apoptosis associated proteins". Molecular Medicine Reports 17, no. 6 (2018): 8101-8110. https://doi.org/10.3892/mmr.2018.8927
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