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
November-2014 Volume 10 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
November-2014 Volume 10 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

Suberoylanilide hydroxamic acid enhances the antitumor activity of oxaliplatin by reversing the oxaliplatin‑induced Src activation in gastric cancer cells

  • Authors:
    • Chenfei Zhou
    • Jun Ji
    • Min Shi
    • Liu Yang
    • Yingyan Yu
    • Bingya Liu
    • Zhenggang Zhu
    • Jun Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Surgery, Shanghai Institute of Digestive Surgery, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
  • Pages: 2729-2735
    |
    Published online on: September 9, 2014
       https://doi.org/10.3892/mmr.2014.2548
  • 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

Oxaliplatin and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA), also known as vorinostat, are potent antitumor agents. The aim of this study was to investigate the effect of SAHA on the antitumor efficacy of oxaliplatin in gastric cancer and the interaction between oxaliplatin and SAHA. Cell growth inhibition was evaluated using Cell Counting Kit‑8 and colony formation assays. Xenografts established in nude mice were used to assess tumor growth in vivo. Western blot analysis was used to detect the expression of acetyl‑histone H3, phosphorylated histone H2AX (γH2AX), B‑cell lymphoma 2 (Bcl‑2), cleaved caspase‑3, cleaved poly (ADP‑ribose) polymerase (PARP), phosphorylated- (p-)Src, Src, Akt and p‑Akt in gastric cancer cells. The in vitro growth of SGC‑7901, Hs746T and MKN28 gastric cancer cells was found to be dose‑dependently inhibited by oxaliplatin and SAHA. Furthermore, combined treatment was observed to be more effective in inhibiting cancer cell growth and colony formation than monotherapy. Similar effects were found in the xenografts. A positive interaction was identified between oxaliplatin and SAHA (between‑subject effects of oxaliplatin and SAHA, P<0.001). In addition, combined exposure to oxaliplatin and SAHA increased γH2AX expression and decreased Bcl‑2 expression. The expression of cleaved caspase‑3 and PARP was also increased with combination treatment. Oxaliplatin‑induced Src phosphorylation was detected in gastric cancer cells, as we have previously reported. However, this effect was inhibited by SAHA. The oxaliplatin‑induced Src phosphorylation was not impaired with Akt inhibition. In conclusion, oxaliplatin and SAHA exhibited a positive interaction when used in combination and were found to suppress gastric cancer cell survival and growth. The reversal of oxaliplatin‑induced Src activation may be responsible for this positive interaction.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Zhao P, Dai M, Chen W and Li N: Cancer trends in China. Jpn J Clin Oncol. 40:281–285. 2010. View Article : Google Scholar

2 

Hartgrink HH, Jansen EP, van Grieken NC and van de Velde CJ: Gastric cancer. Lancet. 374:477–490. 2009. View Article : Google Scholar

3 

Cervantes A, Roda D, Tarazona N, et al: Current questions for the treatment of advanced gastric cancer. Cancer Treat Rev. 39:60–67. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Bang YJ, Van Cutsem E, Feyereislova A, et al: ToGA Trial Investigators: Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 376:687–697. 2010. View Article : Google Scholar

5 

Ohtsu A, Shah MA, Van Cutsem E, et al: Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 29:3968–3976. 2011. View Article : Google Scholar

6 

Lordick F, Kang YK, Chung HC, et al: Arbeitsgemeinschaft Internistische Onkologie and EXPAND Investigators: Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 14:490–499. 2013. View Article : Google Scholar

7 

Waddell T, Chau I, Cunningham D, et al: Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol. 14:481–489. 2013. View Article : Google Scholar

8 

Cunningham D, Starling N, Rao S, et al: Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom: Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 358:36–46. 2008. View Article : Google Scholar

9 

Rabik CA and Dolan ME: Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treat Rev. 33:9–23. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Bang YJ, Kim YW, Yang HK, et al: CLASSIC trial investigators; Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 379:315–321. 2012. View Article : Google Scholar

11 

Shi M, Lou B, Ji J, et al: Synergistic antitumor effects of dasatinib and oxaliplatin in gastric cancer cells. Cancer Chemother Pharmacol. 72:35–44. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Weichert W, Röske A, Gekeler V, et al: Association of patterns of class I histone deacetylase expression with patient prognosis in gastric cancer: a retrospective analysis. Lancet Oncol. 9:139–148. 2008. View Article : Google Scholar

13 

Barneda-Zahonero B and Parra M: Histone deacetylases and cancer. Mol Oncol. 6:579–589. 2012. View Article : Google Scholar

14 

Mann BS, Johnson JR, Cohen MH, et al: FDA approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist. 12:1247–1252. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Carew JS, Giles FJ and Nawrocki ST: Histone deacetylase inhibitors: mechanisms of cell death and promise in combination cancer therapy. Cancer Lett. 269:7–17. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Yoo C, Ryu MH, Na YS, et al: Phase I and pharmacodynamic study of vorinostat combined with capecitabine and cisplatin as first-line chemotherapy in advanced gastric cancer. Invest New Drugs. 32:271–278. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Raymond E, Faivre S, Chaney S, et al: Cellular and molecular pharmacology of oxaliplatin. Mol Cancer Ther. 1:227–235. 2002.

18 

Petruccelli LA, Dupéré-Richer D, Pettersson F, et al: Vorinostat induces reactive oxygen species and DNA damage in acute myeloid leukemia cells. PLoS One. 6:e209872011. View Article : Google Scholar : PubMed/NCBI

19 

Zhang C, Richon V, Ni X, et al: Selective induction of apoptosis by histone deacetylase inhibitor SAHA in cutaneous T-cell lymphoma cells: relevance to mechanism of therapeutic action. J Invest Dermatol. 125:1045–1052. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Chen CS, Weng SC, Tseng PH, et al: Histone acetylation-independent effect of histone deacetylase inhibitors on Akt through the reshuffling of protein phosphatase 1 complexes. J Biol Chem. 280:38879–38887. 2005. View Article : Google Scholar : PubMed/NCBI

21 

Bolden JE, Peart MJ and Johnstone RW: Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov. 5:769–784. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Claerhout S, Lim JY, Choi W, et al: Gene expression signature analysis identifies vorinostat as a candidate therapy for gastric cancer. PLoS One. 6:e246622011. View Article : Google Scholar

23 

Diyabalanage HV, Granda ML and Hooker JM: Combination therapy: histone deacetylase inhibitors and platinum-based chemotherapeutics for cancer. Cancer Lett. 329:1–8. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Rikiishi H, Shinohara F, Sato T, et al: Chemosensitization of oral squamous cell carcinoma cells to cisplatin by histone deacetylase inhibitor, suberoylanilide hydroxamic acid. Int J Oncol. 30:1181–1188. 2007.PubMed/NCBI

25 

Woynarowski JM, Faivre S, Herzig MC, et al: Oxaliplatin-induced damage of cellular DNA. Mol Pharmacol. 58:920–927. 2000.PubMed/NCBI

26 

Faivre S, Chan D, Salinas R, et al: DNA strand breaks and apoptosis induced by oxaliplatin in cancer cells. Biochem Pharmacol. 66:225–237. 2003. View Article : Google Scholar : PubMed/NCBI

27 

Conti C, Leo E, Eichler GS, et al: Inhibition of histone deacetylase in cancer cells slows down replication forks, activates dormant origins, and induces DNA damage. Cancer Res. 70:4470–4480. 2010. View Article : Google Scholar : PubMed/NCBI

28 

New M, Olzscha H and La Thangue NB: HDAC inhibitor-based therapies: can we interpret the code? Mol Oncol. 6:637–656. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Thompson RC, Vardinogiannis I and Gilmore TD: The sensitivity of diffuse large B-cell lymphoma cell lines to histone deacetylase inhibitor-induced apoptosis is modulated by BCL-2 family protein activity. PLoS One. 8:e628222013. View Article : Google Scholar

30 

Hirsch CL, Smith-Windsor EL and Bonham K: Src family kinase members have a common response to histone deacetylase inhibitors in human colon cancer cells. Int J Cancer. 118:547–554. 2006. View Article : Google Scholar

31 

Jiang T and Qiu Y: Interaction between Src and a C-terminal proline-rich motif of Akt is required for Akt activation. J Biol Chem. 278:15789–15793. 2003. View Article : Google Scholar : PubMed/NCBI

32 

Summy JM and Gallick GE: Treatment for advanced tumors: SRC reclaims center stage. Clin Cancer Res. 12:1398–1401. 2006. View Article : Google Scholar : PubMed/NCBI

33 

Hsieh AC, Truitt ML and Ruggero D: Oncogenic AKTivation of translation as a therapeutic target. Br J Cancer. 105:329–336. 2011. View Article : Google Scholar : PubMed/NCBI

34 

Liu J, Fu XQ, Zhou W, et al: LY294002 potentiates the anti-cancer effect of oxaliplatin for gastric cancer via death receptor pathway. World J Gastroenterol. 17:181–190. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhou C, Ji J, Shi M, Yang L, Yu Y, Liu B, Zhu Z and Zhang J: Suberoylanilide hydroxamic acid enhances the antitumor activity of oxaliplatin by reversing the oxaliplatin‑induced Src activation in gastric cancer cells. Mol Med Rep 10: 2729-2735, 2014.
APA
Zhou, C., Ji, J., Shi, M., Yang, L., Yu, Y., Liu, B. ... Zhang, J. (2014). Suberoylanilide hydroxamic acid enhances the antitumor activity of oxaliplatin by reversing the oxaliplatin‑induced Src activation in gastric cancer cells. Molecular Medicine Reports, 10, 2729-2735. https://doi.org/10.3892/mmr.2014.2548
MLA
Zhou, C., Ji, J., Shi, M., Yang, L., Yu, Y., Liu, B., Zhu, Z., Zhang, J."Suberoylanilide hydroxamic acid enhances the antitumor activity of oxaliplatin by reversing the oxaliplatin‑induced Src activation in gastric cancer cells". Molecular Medicine Reports 10.5 (2014): 2729-2735.
Chicago
Zhou, C., Ji, J., Shi, M., Yang, L., Yu, Y., Liu, B., Zhu, Z., Zhang, J."Suberoylanilide hydroxamic acid enhances the antitumor activity of oxaliplatin by reversing the oxaliplatin‑induced Src activation in gastric cancer cells". Molecular Medicine Reports 10, no. 5 (2014): 2729-2735. https://doi.org/10.3892/mmr.2014.2548
Copy and paste a formatted citation
x
Spandidos Publications style
Zhou C, Ji J, Shi M, Yang L, Yu Y, Liu B, Zhu Z and Zhang J: Suberoylanilide hydroxamic acid enhances the antitumor activity of oxaliplatin by reversing the oxaliplatin‑induced Src activation in gastric cancer cells. Mol Med Rep 10: 2729-2735, 2014.
APA
Zhou, C., Ji, J., Shi, M., Yang, L., Yu, Y., Liu, B. ... Zhang, J. (2014). Suberoylanilide hydroxamic acid enhances the antitumor activity of oxaliplatin by reversing the oxaliplatin‑induced Src activation in gastric cancer cells. Molecular Medicine Reports, 10, 2729-2735. https://doi.org/10.3892/mmr.2014.2548
MLA
Zhou, C., Ji, J., Shi, M., Yang, L., Yu, Y., Liu, B., Zhu, Z., Zhang, J."Suberoylanilide hydroxamic acid enhances the antitumor activity of oxaliplatin by reversing the oxaliplatin‑induced Src activation in gastric cancer cells". Molecular Medicine Reports 10.5 (2014): 2729-2735.
Chicago
Zhou, C., Ji, J., Shi, M., Yang, L., Yu, Y., Liu, B., Zhu, Z., Zhang, J."Suberoylanilide hydroxamic acid enhances the antitumor activity of oxaliplatin by reversing the oxaliplatin‑induced Src activation in gastric cancer cells". Molecular Medicine Reports 10, no. 5 (2014): 2729-2735. https://doi.org/10.3892/mmr.2014.2548
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