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
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
May-2018 Volume 15 Issue 5

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
May-2018 Volume 15 Issue 5

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

Bufalin and 5‑fluorouracil synergistically induce apoptosis in colorectal cancer cells

  • Authors:
    • Xiao‑Yu Dai
    • Bao‑Feng Zhou
    • Yang‑Yang Xie
    • Jie Lou
    • Ke‑Qiang Li
  • View Affiliations / Copyright

    Affiliations: Department of Anorectal Surgery, Clinical Research Center, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315010, P.R. China, Department of Digestion, Clinical Research Center, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315010, P.R. China, Key Laboratory of Molecular Biology of Cancer, Clinical Research Center, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315010, P.R. China
  • Pages: 8019-8026
    |
    Published online on: March 23, 2018
       https://doi.org/10.3892/ol.2018.8332
  • 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

5‑fluorouracil (5‑FU) has been used in the treatment of colorectal cancer for >50 years. However, drug resistance remains an obstacle in the application of 5‑FU‑based chemotherapy. Bufalin, a type of steroid with anti‑tumor activity, may be purified from the skin and parotid venom glands of toads. In order to improve the anti‑tumor effect of 5‑FU, the present study examined the combined effects of bufalin with 5‑FU on human colorectal cancer HCT116 cells. Following treatment, cell proliferation was quantified using MTT assay and apoptotic cell percentage was assessed by flow cytometry. The apoptosis‑associated protein expression was evaluated by western blotting. It was observed that bufalin enhanced the cytotoxicity of 5‑FU in HCT116 cells via the induction of the mitochondrial apoptotic pathway. Additionally, bufalin combined with 5‑FU reduced the expression levels of anti‑apoptotic proteins, such as Mcl‑1, XIAP and Bcl‑2 and upregulated the levels of the pro‑apoptotic proteins, Bax and Bad. To verify the role of Bax, RNA interference was used to knock‑down Bax. It was determined that the synergistic effect between 5‑FU and bufalin was diminished following the silencing of Bax. In summary, bufalin in combination with 5‑FU may induce a higher level of apoptosis compared with monotherapy, and the combination mat be a potential therapeutic strategy for the treatment of colorectal cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Torre LA, Siegel RL, Ward EM and Jemal A: Global cancer incidence and mortality rates and trends-an update. Cancer Epidemiol Biomarkers Prev. 25:16–27. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Mayer RJ: Targeted therapy for advanced colorectal cancer-more is not always better. N Engl J Med. 360:623–625. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Longley DB, Harkin DP and Johnston PG: 5-fluorouracil: Mechanisms of action and clinical strategies. Nat Rev Cancer. 3:330–338. 2003. View Article : Google Scholar : PubMed/NCBI

5 

Temraz S, Mukherji D, Alameddine R and Shamseddine A: Methods of overcoming treatment resistance in colorectal cancer. Crit Rev Oncol Hematol. 89:217–230. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Yu R, Deedigan L, Albarenque SM, Mohr A and Zwacka RM: Delivery of sTRAIL variants by MSCs in combination with cytotoxic drug treatment leads to p53-independent enhanced antitumor effects. Cell Death Dis. 4:e5032013. View Article : Google Scholar : PubMed/NCBI

7 

Rich JN and Bao S: Chemotherapy and cancer stem cells. Cell Stem Cell. 1:353–355. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Tummers B and Green DR: Caspase-8: Regulating life and death. Immunol Rev. 277:76–89. 2017. View Article : Google Scholar : PubMed/NCBI

9 

Estaquier J, Vallette F, Vayssiere JL and Mignotte B: The mitochondrial pathways of apoptosis. Adv Exp Med Biol. 942:157–183. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, Mangion J, Jacotot E, Costantini P, Loeffler M, et al: Molecular characterization of mitochondrial apoptosis-inducing factor. Nature. 397:441–446. 1999. View Article : Google Scholar : PubMed/NCBI

11 

Azmi AS, Wang Z, Philip PA, Mohammad RM and Sarkar FH: Emerging Bcl-2 inhibitors for the treatment of cancer. Expert Opin Emerg Drugs. 16:59–70. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Shakibaei M, Mobasheri A, Lueders C, Busch F, Shayan P and Goel A: Curcumin enhances the effect of chemotherapy against colorectal cancer cells by inhibition of NF-κB and Src protein kinase signaling pathways. PLoS One. 8:e572182013. View Article : Google Scholar : PubMed/NCBI

13 

Douillard JY, Sobrero A, Carnaghi C, Comella P, Díaz-Rubio E, Santoro A and Van Cutsem E: Metastatic colorectal cancer: Integrating irinotecan into combination and sequential chemotherapy. Ann Oncol. 14 Suppl 2:ii7–ii12. 2003. View Article : Google Scholar : PubMed/NCBI

14 

Giacchetti S, Perpoint B, Zidani R, Le Bail N, Faggiuolo R, Focan C, Chollet P, Llory JF, Letourneau Y, Coudert B, et al: Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol. 18:136–147. 2000. View Article : Google Scholar : PubMed/NCBI

15 

Lu CX, Nan KJ and Lei Y: Agents from amphibians with anticancer properties. Anticancer Drugs. 19:931–939. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Miao Q, Bi LL, Li X, Miao S, Zhang J, Zhang S, Yang Q, Xie YH, Zhang J and Wang SW: Anticancer effects of bufalin on human hepatocellular carcinoma HepG2 cells: Roles of apoptosis and autophagy. Int J Mol Sci. 14:1370–1382. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Xie CM, Chan WY, Yu S, Zhao J and Cheng CH: Bufalin induces autophagy-mediated cell death in human colon cancer cells through reactive oxygen species generation and JNK activation. Free Radic Biol Med. 51:1365–1375. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Santandreu FM, Valle A, Oliver J and Roca P: Resveratrol potentiates the cytotoxic oxidative stress induced by chemotherapy in human colon cancer cells. Cell Physiol Biochem. 28:219–228. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Fishbein AB, Wang CZ, Li XL, Mehendale SR, Sun S, Aung HH and Yuan CS: Asian ginseng enhances the anti-proliferative effect of 5-fluorouracil on human colorectal cancer: Comparison between white and red ginseng. Arch Pharm Res. 32:505–513. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Jiang L, Zhao MN, Liu TY, Wu XS, Weng H, Ding Q, Shu YJ, Bao RF, Li ML, Mu JS, et al: Bufalin induces cell cycle arrest and apoptosis in gallbladder carcinoma cells. Tumour Biol. 35:10931–10941. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Qiu DZ, Zhang ZJ, Wu WZ and Yang YK: Bufalin, a component in Chansu, inhibits proliferation and invasion of hepatocellular carcinoma cells. BMC Complement Altern Med. 13:1852013. View Article : Google Scholar : PubMed/NCBI

22 

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

23 

Chang Y, Zhao Y, Gu W, Cao Y, Wang S, Pang J and Shi Y: Bufalin inhibits the differentiation and proliferation of cancer stem cells derived from primary osteosarcoma cells through Mir-148a. Cell Physiol Biochem. 36:1186–1196. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Zhao L, Liu S, Che X, Hou K, Ma Y, Li C, Wen T, Fan Y, Hu X, Liu Y and Qu X: Bufalin inhibits TGF-β-induced epithelial-to-mesenchymal transition and migration in human lung cancer A549 cells by downregulating TGF-β receptors. Int J Mol Med. 36:645–652. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Sampath D, Rao VA and Plunkett W: Mechanisms of apoptosis induction by nucleoside analogs. Oncogene. 22:9063–9074. 2003. View Article : Google Scholar : PubMed/NCBI

26 

Hong SH and Choi YH: Bufalin induces apoptosis through activation of both the intrinsic and extrinsic pathways in human bladder cancer cells. Oncol Rep. 27:114–120. 2012.PubMed/NCBI

27 

Datta SR, Katsov A, Hu L, Petros A, Fesik SW, Yaffe MB and Greenberg ME: 14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation. Mol Cell. 6:41–51. 2000. View Article : Google Scholar : PubMed/NCBI

28 

Qu Y, Xia P, Zhang S, Pan S and Zhao J: Silencing XIAP suppresses osteosarcoma cell growth, and enhances the sensitivity of osteosarcoma cells to doxorubicin and cisplatin. Oncol Rep. 33:1177–1184. 2015. View Article : Google Scholar : PubMed/NCBI

29 

Mehrotra S, Languino LR, Raskett CM, Mercurio AM, Dohi T and Altieri DC: IAP regulation of metastasis. Cancer Cell. 17:53–64. 2010. View Article : Google Scholar : PubMed/NCBI

30 

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

31 

Meng Z, Yang P, Shen Y, Bei W, Zhang Y, Ge Y, Newman RA, Cohen L, Liu L, Thornton B, et al: Pilot study of huachansu in patients with hepatocellular carcinoma, nonsmall-cell lung cancer, or pancreatic cancer. Cancer. 115:5309–5318. 2009. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Dai XY, Zhou BF, Xie YY, Lou J and Li KQ: Bufalin and 5‑fluorouracil synergistically induce apoptosis in colorectal cancer cells. Oncol Lett 15: 8019-8026, 2018.
APA
Dai, X., Zhou, B., Xie, Y., Lou, J., & Li, K. (2018). Bufalin and 5‑fluorouracil synergistically induce apoptosis in colorectal cancer cells. Oncology Letters, 15, 8019-8026. https://doi.org/10.3892/ol.2018.8332
MLA
Dai, X., Zhou, B., Xie, Y., Lou, J., Li, K."Bufalin and 5‑fluorouracil synergistically induce apoptosis in colorectal cancer cells". Oncology Letters 15.5 (2018): 8019-8026.
Chicago
Dai, X., Zhou, B., Xie, Y., Lou, J., Li, K."Bufalin and 5‑fluorouracil synergistically induce apoptosis in colorectal cancer cells". Oncology Letters 15, no. 5 (2018): 8019-8026. https://doi.org/10.3892/ol.2018.8332
Copy and paste a formatted citation
x
Spandidos Publications style
Dai XY, Zhou BF, Xie YY, Lou J and Li KQ: Bufalin and 5‑fluorouracil synergistically induce apoptosis in colorectal cancer cells. Oncol Lett 15: 8019-8026, 2018.
APA
Dai, X., Zhou, B., Xie, Y., Lou, J., & Li, K. (2018). Bufalin and 5‑fluorouracil synergistically induce apoptosis in colorectal cancer cells. Oncology Letters, 15, 8019-8026. https://doi.org/10.3892/ol.2018.8332
MLA
Dai, X., Zhou, B., Xie, Y., Lou, J., Li, K."Bufalin and 5‑fluorouracil synergistically induce apoptosis in colorectal cancer cells". Oncology Letters 15.5 (2018): 8019-8026.
Chicago
Dai, X., Zhou, B., Xie, Y., Lou, J., Li, K."Bufalin and 5‑fluorouracil synergistically induce apoptosis in colorectal cancer cells". Oncology Letters 15, no. 5 (2018): 8019-8026. https://doi.org/10.3892/ol.2018.8332
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