Histone deacetylase inhibitor, suberoylanilide hydroxamic acid (Vorinostat, SAHA) profoundly inhibits the growth of human pancreatic cancer cells - PubMed (original) (raw)

. 2007 Aug 1;121(3):656-65.

doi: 10.1002/ijc.22558.

Affiliations

• PMID: 17417771
• DOI: 10.1002/ijc.22558

Histone deacetylase inhibitor, suberoylanilide hydroxamic acid (Vorinostat, SAHA) profoundly inhibits the growth of human pancreatic cancer cells

Takashi Kumagai et al. Int J Cancer. 2007.

Abstract

Tumor suppressor genes are often silenced in human cancer; this can occur by transcriptional repression by deacetylation in the promoter regions, mediated by histone deacetylase (HDAC). HDAC inhibitors can block cancer cell growth by restoring expression of tumor suppressor genes. In this study, we investigated the effects of a HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA) on pancreatic cancer cells. SAHA inhibited the growth of 6 pancreatic cancer cell lines in a dose-dependent manner as measured by MTT and clonogenic assays (ED(50) approximately 10(-6) M) associated with induction of apoptosis, G2 cell cycle arrest and also induced differentiation as indicated by morphology and increased expression of cytokeratin 7. It increased expression of p21(WAF1) (independent of the mutational status of p53), C/EBPalpha, RARalpha and E-cadherin; these genes have been associated with decreased proliferation in other cancers. SAHA decreased cyclin B1 expression; this cyclin normally promotes progression through G2 of the cell cycle. SAHA mediated acetylation of histone H3 globally, as well as, associated with the p21(WAF1) promoter, as measured by chromatin immunoprecipitation. SAHA also decreased levels of c-myc and cyclin D1, independent of an active beta-catenin pathway. In further studies, the combination of SAHA and an inhibitor of DNA methylation, 5-Aza-2'-deoxycytidine, had an enhanced antiproliferative effect on pancreatic cancer cells. In summary, SAHA inhibited the growth of human pancreatic cancer cells by inducing apoptosis, differentiation and cell cycle arrest, as well as increase in the expression of several tumor suppressor genes. SAHA is a novel, promising therapeutic agent for human pancreatic cancers.

Copyright (c) 2007 Wiley-Liss, Inc.

PubMed Disclaimer

Similar articles

• Histone deacetylase inhibitors profoundly decrease proliferation of human lymphoid cancer cell lines.
  Sakajiri S, Kumagai T, Kawamata N, Saitoh T, Said JW, Koeffler HP. Sakajiri S, et al. Exp Hematol. 2005 Jan;33(1):53-61. doi: 10.1016/j.exphem.2004.09.008. Exp Hematol. 2005. PMID: 15661398
• Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor: effects on gene expression and growth of glioma cells in vitro and in vivo.
  Yin D, Ong JM, Hu J, Desmond JC, Kawamata N, Konda BM, Black KL, Koeffler HP. Yin D, et al. Clin Cancer Res. 2007 Feb 1;13(3):1045-52. doi: 10.1158/1078-0432.CCR-06-1261. Clin Cancer Res. 2007. PMID: 17289901
• Histone Deacetylase (HDAC) Inhibitor, Suberoylanilide Hydroxamic Acid (SAHA), Induces Apoptosis in Prostate Cancer Cell Lines via the Akt/FOXO3a Signaling Pathway.
  Shi XY, Ding W, Li TQ, Zhang YX, Zhao SC. Shi XY, et al. Med Sci Monit. 2017 Dec 6;23:5793-5802. doi: 10.12659/msm.904597. Med Sci Monit. 2017. PMID: 29211704 Free PMC article.
• Novel hydroxamate and anilide derivatives as potent histone deacetylase inhibitors: synthesis and antiproliferative evaluation.
  Bouchain G, Delorme D. Bouchain G, et al. Curr Med Chem. 2003 Nov;10(22):2359-72. doi: 10.2174/0929867033456585. Curr Med Chem. 2003. PMID: 14529479 Review.
• The interaction of histone deacetylase inhibitors and DNA methyltransferase inhibitors in the treatment of human cancer cells.
  Zhu WG, Otterson GA. Zhu WG, et al. Curr Med Chem Anticancer Agents. 2003 May;3(3):187-99. doi: 10.2174/1568011033482440. Curr Med Chem Anticancer Agents. 2003. PMID: 12769777 Review.

Cited by

• Experimental in vivo and in vitro treatment with a new histone deacetylase inhibitor belinostat inhibits the growth of pancreatic cancer.
  Dovzhanskiy DI, Arnold SM, Hackert T, Oehme I, Witt O, Felix K, Giese N, Werner J. Dovzhanskiy DI, et al. BMC Cancer. 2012 Jun 8;12:226. doi: 10.1186/1471-2407-12-226. BMC Cancer. 2012. PMID: 22681698 Free PMC article.
• Epigenetics of neurological cancers.
  Fouse SD, Costello JF. Fouse SD, et al. Future Oncol. 2009 Dec;5(10):1615-29. doi: 10.2217/fon.09.132. Future Oncol. 2009. PMID: 20001799 Free PMC article. Review.
• Chemistry, biology, and QSAR studies of substituted biaryl hydroxamates and mercaptoacetamides as HDAC inhibitors-nanomolar-potency inhibitors of pancreatic cancer cell growth.
  Kozikowski AP, Chen Y, Gaysin AM, Savoy DN, Billadeau DD, Kim KH. Kozikowski AP, et al. ChemMedChem. 2008 Mar;3(3):487-501. doi: 10.1002/cmdc.200700314. ChemMedChem. 2008. PMID: 18181121 Free PMC article.
• Anti-tumor effect in human lung cancer by a combination treatment of novel histone deacetylase inhibitors: SL142 or SL325 and retinoic acids.
  Han S, Fukazawa T, Yamatsuji T, Matsuoka J, Miyachi H, Maeda Y, Durbin M, Naomoto Y. Han S, et al. PLoS One. 2010 Nov 4;5(11):e13834. doi: 10.1371/journal.pone.0013834. PLoS One. 2010. PMID: 21079797 Free PMC article.
• Molecular epigenetics and genetics in neuro-oncology.
  Nagarajan RP, Costello JF. Nagarajan RP, et al. Neurotherapeutics. 2009 Jul;6(3):436-46. doi: 10.1016/j.nurt.2009.04.002. Neurotherapeutics. 2009. PMID: 19560734 Free PMC article. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Wiley

• Other Literature Sources

  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal