The effect of combined treatment with cisplatin and histone deacetylase inhibitors on HeLa cells.
10.3802/jgo.2010.21.4.262
- Author:
Ke Long JIN
1
;
Jeong Yeol PARK
;
Eun Joo NOH
;
Kwang Lae HOE
;
Joo Hak LEE
;
Jong Hyeok KIM
;
Joo Hyun NAM
Author Information
1. Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. jhnam@amc.seoul.kr
- Publication Type:Original Article
- Keywords:
Cervical cancer;
Apoptosis;
Cisplatin;
Suberoylanilide hydroxamic acid;
Sirtinol
- MeSH:
Apoptosis;
Benzamides;
Caspase 3;
Cell Proliferation;
Chromatin;
Cisplatin;
DNA;
Down-Regulation;
HeLa Cells;
Histone Deacetylase Inhibitors;
Histone Deacetylases;
Histones;
Humans;
Hydroxamic Acids;
Indoles;
Naphthols;
Proteins;
Relaxation;
Uterine Cervical Neoplasms;
X-Linked Inhibitor of Apoptosis Protein
- From:Journal of Gynecologic Oncology
2010;21(4):262-268
- CountryRepublic of Korea
- Language:English
-
Abstract:
OBJECTIVE: To investigate the combined effects of cisplatin and the histone deacetylase (HDAC) inhibitors suberoylanilide hydroxamic acid (SAHA) or sirtinol on HeLa cells and assess the mechanism underlying HDAC inhibitor-cisplatin synergy. METHODS: The antineoplastic actions of cisplatin, SAHA and sirtinol, alone and in combination, were evaluated using the tetrazolium dye-based MTT cell proliferation assay, DAPI nuclear staining and cytotoxicity analysis. RESULTS: Exposure to cisplatin, SAHA or sirtinol alone induced a dose-dependent reduction in HeLa cell viability. Combined treatment with cisplatin and SAHA or sirtinol was significantly more cytotoxic than cisplatin alone. Individually, cisplatin, SAHA and sirtinol activated caspase-3 and induced apoptosis, but the effects of combined treatment were greater. Importantly, both HDAC inhibitors dose-dependently inhibited the expression of the antiapoptotic proteins Bcl-2 and x-linked inhibitor of apoptosis protein (XIAP). CONCLUSION: The combination of cisplatin and SAHA or sirtinol had synergistic effect on the HeLa cell viability. This potentiation of cisplatin activity was associated with HDAC inhibitor-mediated down-regulation of Bcl-2 and XIAP. These may result from the relaxation of chromatin by these HDAC inhibitors that increase cisplatin sensitivity by enhancing the accessibility of DNA to cisplatin and transcriptional regulators.
