The effect of combined treatment with cisplatin and histone deacetylase inhibitors on HeLa cells / 부인종양
Journal of Gynecologic Oncology
;
: 262-268, 2010.
Article
in English
| WPRIM
| ID: wpr-6890
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Relaxation
/
Benzamides
/
DNA
/
Chromatin
/
HeLa Cells
/
Histones
/
Proteins
/
Down-Regulation
/
Uterine Cervical Neoplasms
/
Cisplatin
Limits:
Humans
Language:
English
Journal:
Journal of Gynecologic Oncology
Year:
2010
Type:
Article
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