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
January-2019 Volume 17 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-2019 Volume 17 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
Article

Enhanced cytotoxicity of human hepatocellular carcinoma cells following pretreatment with sorafenib combined with trichostatin A

  • Authors:
    • John Chun‑Hao Chen
    • Hui‑Yen Chuang
    • Yi‑Jen Liao
    • Fei‑Ting Hsu
    • Yen‑Chung Chen
    • Wei‑Hsun Wang
    • Jeng‑Jong Hwang
  • View Affiliations / Copyright

    Affiliations: Department of Biomedical Imaging and Radiological Sciences, National Yang Ming University, Taipei 112, Taiwan, R.O.C., School of Medical Laboratory and Biotechnology, Taipei Medical University, Taipei 110, Taiwan, R.O.C., Department of Medical Imaging, Taipei Medical University Hospital, Taipei 110, Taiwan, R.O.C., Department of Pathology, National Yang Ming University Hospital, Yilan 260, Taiwan, R.O.C., Department of Orthopedic Surgery, Changhua Christian Hospital, Changhua 500, Taiwan, R.O.C.
  • Pages: 638-645
    |
    Published online on: October 16, 2018
       https://doi.org/10.3892/ol.2018.9582
  • 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

Trichostatin A (TSA), a hydroxamate histone deacetylase inhibitor, is a compound that has been identified to induce anticancer activity. The aim of the present study was to investigate whether sorafenib, in combination with TSA, was able to augment the anticancer effects of TSA, identifying an optimum treatment time plan and the potential underlying molecular mechanisms involved in human hepatocellular carcinoma (HCC) in vitro. Huh7/nuclear factor‑κB (NF‑κB)‑luc2 cells were treated with TSA or sorafenib alone, or sorafenib, prior to, in combination with or following TSA treatment. Huh7/NF‑κB‑luc2 cell viability following TSA treatment was determined using an MTT assay, and NF‑κB activity was analyzed. In addition, the expression levels of NF‑κB‑regulated downstream effector proteins were assayed by western blotting. Inhibitors of mitogen‑activated protein kinases (MAPKs), protein kinase B (AKT) and mutant inhibitor of NF‑κBα (IκBαM) vectors were used to confirm the function of the NF‑κB signal transduction pathways in response to the effects of sorafenib combined with TSA against HCC. The results of the present study indicated that pre‑treatment with sorafenib followed by TSA inhibited the cell viability compared with other treatment modalities, and prevented TSA‑induced extracellular‑signal‑regulated kinase (ERK)/NF‑κB activity and expression of downstream effector proteins. It was further demonstrated that IκBαM vector sensitized Huh7/NF‑κB‑luc2 cells to TSA, thus it was possible to reverse TSA‑induced NF‑κB activity using PD98059, a MAPK/ERK kinase inhibitor. In conclusion, sorafenib pre‑treatment may increase the efficacy of subsequent TSA treatment in HCC. Furthermore, sorafenib pre‑treatment is hypothesized to sensitize HCC to TSA via the inhibition of the MEK/ERK/NF‑κB signal transduction pathway.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Pan LN, Lu J and Huang B: HDAC inhibitors: A potential new category of anti-tumor agents. Cell Mol Immunol. 4:337–343. 2007.PubMed/NCBI

2 

Mund C and Lyko F: Epigenetic cancer therapy: Proof of concept and remaining challenges. Bioessays. 32:949–957. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Rosato RR, Almenara JA and Grant S: The histone deacetylase inhibitor MS-275 promotes differentiation or apoptosis in human leukemia cells through a process regulated by generation of reactive oxygen species and induction of p21CIP1/WAF1. Cancer Res. 63:3637–3645. 2003.PubMed/NCBI

4 

Baradari V, Höpfner M, Huether A, Schuppan D and Scherubl H: Histone deacetylase inhibitor MS-275 alone or combined with bortezomib or sorafenib exhibits strong antiproliferative action in human cholangiocarcinoma cells. World J Gastroenterol. 13:4458–4466. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Ngamphaiboon N, Dy GK, Ma WW, Zhao Y, Reungwetwattana T, DePaolo D, Ding Y, Brady W, Fetterly G and Adjei AA: A phase I study of the histone deacetylase (HDAC) inhibitor entinostat, in combination with sorafenib in patients with advanced solid tumors. Invest New Drugs. 33:225–232. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Yuan H, Li AJ, Ma SL, Cui LJ, Wu B, Yin L and Wu MC: Inhibition of autophagy significantly enhances combination therapy with sorafenib and HDAC inhibitors (vorinostatin) for human hepatoma cells. World J Gastroenterol. 20:4953–4962. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Huang HL, Lee HY, Tsai AC, Peng CY, Lai MJ, Wang JC, Pan SL, Teng CM and Liou JP: Anticancer activity of MPT0E028, a novel potent histone deacetylase inhibitor, in human colorectal cancer HCT116 cells in vitro and in vivo. PLoS One. 7:e436452012. View Article : Google Scholar : PubMed/NCBI

8 

Chen CH, Chen MC, Wang JC, Tsai AC, Chen CS, Liou JP, Pan SL and Teng CM: Synergistic interaction between the HDAC inhibitor, MPT0E028 and sorafenib in liver cancer cells in vitro and in vivo. Clin Cancer Res. 20:1274–1287. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Yao J, Duan L, Fan M and Wu X: NF-kappaB signaling pathway is involved in growth inhibition, G2/M arrest and apoptosis induced by trichostatin A in human tongue carcinoma cells. Pharmaco Res. 54:406–413. 2006.

10 

Zhang G, Park MA, Mitchell C, Hamed H, Rahmani M, Martin AP, Curiel DT, Yacoub A, Graf M, Lee R, et al: Vorinostat and sorafenib synergistically kill tumor cells via FLIP suppression and CD95 activation. Clin Cancer Res. 14:5385–5399. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Duvic M and Vu J: Update on the treatment of cutaneous T-cell lymphoma (CTCL): Focus on vorinostat. Biol Targets Ther. 1:377–392. 2007.

12 

Coradini D and Speranza A: Histone deacetylase inhibitors for treatment of hepatocellular carcinoma. Acta pharmacol Sin. 26:1025–1033. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Yan G, Graham K and Lanza-Jacoby S: Curcumin enhances the anticancer effects of trichostatin a in breast cancer cells. Mol Carcinogen. 52:404–411. 2013. View Article : Google Scholar

14 

Yao J, Qian CJ, Ye B, Zhang X and Liang Y: ERK inhibition enhances TSA-induced gastric cancer cell apoptosis via NF-κB-dependent and Notch-independent mechanism. Life Sci. 91:186–193. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Tai DI, Tsai SL, Chang YH, Huang SN, Chen TC, Chang KS and Liaw YF: Constitutive activation of nuclear factor kappaB in hepatocellular carcinoma. Cancer. 89:2274–2281. 2000. View Article : Google Scholar : PubMed/NCBI

16 

Li W, Tan D, Zenali MJ and Brown RE: Constitutive activation of nuclear factor-kappa B (NF-κB) signaling pathway in fibrolamellar hepatocellular carcinoma. Int J Clin Exp Patho. 3:238–243. 2010.

17 

Wang WH, Chiang IT, Liu YC, Hsu FT, Chen HW, Chen CL, Lee YJ, Lin WJ and Hwang JJ: Simultaneous imaging of temporal changes of NF-κB activity and viable tumor cells in Huh7/NF-kappaB-tk-luc2/rfp tumor-bearing mice. In Vivo. 27:339–350. 2013.PubMed/NCBI

18 

Pan CC, Kavanagh BD, Dawson LA, LI XA, Das SK, Miften M and Tan RK: Radiation-associated liver injury. Int J Radiat Oncol. 76 Suppl:S94–S100. 2010. View Article : Google Scholar

19 

Liu YC, Chiang IT, Hsu FT and Hwang JJ: Using NF-κB as a molecular target for theranostics in radiation oncology research. Expert Rev Mol Diagn. 12:139–146. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Dai Y, Guzman ML, Chen S, Wang L, Yeung SK, Pei XY, Dent P, Jordan CT and Grant S: The NF (Nuclear factor)-kappaB inhibitor parthenolide interacts with histone deacetylase inhibitors to induce MKK7/JNK1-dependent apoptosis in human acute myeloid leukaemia cells. Brit J Haematol. 151:70–83. 2010. View Article : Google Scholar

21 

Hsu FT, Liu YC, Chiang IT, Liu RS, Wang HE, Lin WJ and Hwang JJ: Sorafenib increases efficacy of vorinostat against human hepatocellular carcinoma through transduction inhibition of vorinostat-induced ERK/NF-κB signaling. Int J Oncol. 45:177–188. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Chiang IT, Liu YC, Wang WH, Hsu FT, Chen HW, Lin WJ, Chang WY and Hwang JJ: Sorafenib inhibits TPA-induced MMP-9 and VEGF expression via suppression of ERK/NF-κB pathway in hepatocellular carcinoma cells. In Vivo. 26:671–681. 2012.PubMed/NCBI

23 

Kuo YC, Lin WC, Chiang IT, Chang YF, Chen CW, Su SH, Chen CL and Hwang JJ: Sorafenib sensitizes human colorectal carcinoma to radiation via suppression of NF-κB expression in vitro and in vivo. Biomed Pharmacother. 66:12–20. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Meidhof S, Brabletz S, Lehmann W, Preca BT, Mock K, Ruh M, Schüler J, Berthold M, Weber A, Burk U, et al: ZEB-1 associated drug resistance in cancer cells is reversed by class I HDAC inhibitor mocetinostat. EMBO Mol Med. 7:831–847. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Rundall BK, Denlinger CE and Jones DR: Combined histone deacetylase and NF-kappaB inhibition sensitizes non-small cell lung cancer to cell death. Surgery. 136:416–425. 2004. View Article : Google Scholar : PubMed/NCBI

26 

Domingo-Domenech J, Pippa R, Tapia M, Gascon P, Bachs O and Bosch M: Inactivation of NF-kappaB by proteasome inhibition contributes to increased apoptosis induced by histone deacetylase inhibitors in human breast cancer cells. Breast Cancer Res Tr. 112:53–62. 2008. View Article : Google Scholar

27 

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

28 

Li Q, Hu Y, Xi M, He L, Zhao L and Liu M: Sorafenib modulates the radiosensitivity of hepatocellular carcinoma cells in vitro in a schedule-dependent manner. BMC Cancer. 12:4852012. View Article : Google Scholar : PubMed/NCBI

29 

Yu W, Gu K, Yu Z, Yuan D, He M, Ma N, Lai S, Zhao J, Ren Z, Zhang X, et al: Sorafenib potentiates irradiation effect in hepatocellular carcinoma in vitro and in vivo. Cancer Lett. 329:109–117. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Chen J CH, Chuang HY, Hsu FT, Chen YC, Chien YC and Hwang JJ: Sorafenib pretreatment enhances radiotherapy through targeting MEK/ERK/NF-κB pathway in human hepatocellular carcinoma-bearing mouse model. Oncotarget. 2016.(in press).

31 

Komarova NL, Katouli AA and Wodarz D: Combination of two but not three current targeted drugs can improve therapy of chronic myeloid leukemia. PLoS One. 4:e44232019. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Chen JC, Chuang HY, Liao YJ, Hsu FT, Chen YC, Wang WH and Hwang JJ: Enhanced cytotoxicity of human hepatocellular carcinoma cells following pretreatment with sorafenib combined with trichostatin A. Oncol Lett 17: 638-645, 2019.
APA
Chen, J.C., Chuang, H., Liao, Y., Hsu, F., Chen, Y., Wang, W., & Hwang, J. (2019). Enhanced cytotoxicity of human hepatocellular carcinoma cells following pretreatment with sorafenib combined with trichostatin A. Oncology Letters, 17, 638-645. https://doi.org/10.3892/ol.2018.9582
MLA
Chen, J. C., Chuang, H., Liao, Y., Hsu, F., Chen, Y., Wang, W., Hwang, J."Enhanced cytotoxicity of human hepatocellular carcinoma cells following pretreatment with sorafenib combined with trichostatin A". Oncology Letters 17.1 (2019): 638-645.
Chicago
Chen, J. C., Chuang, H., Liao, Y., Hsu, F., Chen, Y., Wang, W., Hwang, J."Enhanced cytotoxicity of human hepatocellular carcinoma cells following pretreatment with sorafenib combined with trichostatin A". Oncology Letters 17, no. 1 (2019): 638-645. https://doi.org/10.3892/ol.2018.9582
Copy and paste a formatted citation
x
Spandidos Publications style
Chen JC, Chuang HY, Liao YJ, Hsu FT, Chen YC, Wang WH and Hwang JJ: Enhanced cytotoxicity of human hepatocellular carcinoma cells following pretreatment with sorafenib combined with trichostatin A. Oncol Lett 17: 638-645, 2019.
APA
Chen, J.C., Chuang, H., Liao, Y., Hsu, F., Chen, Y., Wang, W., & Hwang, J. (2019). Enhanced cytotoxicity of human hepatocellular carcinoma cells following pretreatment with sorafenib combined with trichostatin A. Oncology Letters, 17, 638-645. https://doi.org/10.3892/ol.2018.9582
MLA
Chen, J. C., Chuang, H., Liao, Y., Hsu, F., Chen, Y., Wang, W., Hwang, J."Enhanced cytotoxicity of human hepatocellular carcinoma cells following pretreatment with sorafenib combined with trichostatin A". Oncology Letters 17.1 (2019): 638-645.
Chicago
Chen, J. C., Chuang, H., Liao, Y., Hsu, F., Chen, Y., Wang, W., Hwang, J."Enhanced cytotoxicity of human hepatocellular carcinoma cells following pretreatment with sorafenib combined with trichostatin A". Oncology Letters 17, no. 1 (2019): 638-645. https://doi.org/10.3892/ol.2018.9582
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