Mechanism of apoptosis induced by SIRT1 deacetylase inhibitors in human breast cancer MCF-7 drug-resistant cells / 药学学报
Acta Pharmaceutica Sinica
;
(12): 1003-1010, 2008.
Article
in Chinese
| WPRIM
| ID: wpr-232652
ABSTRACT
The mechanism of apoptosis induced by SIRT1 deacetylase inhibitors in both human breast cancer MCF-7 and MCF-7 doxorubicin-resistant cells was studied. MTT assay was used to detect growth-inhibitory effect on the cells. Protein expression was detected by Western blotting. Chromatin condensation was detected by a fluorescent microscope after Hoechst 33342 staining. Cell cycle distribution was analyzed with flow cytometry. Apoptotic cells were detected with Annexin V staining. Nicotinamide (NAM) and Sirtinol, two SIRT1 deacetylase inhibitors, exhibited the similar growth-inhibitory effects on MCF-7/DOX cells and MCF-7 cells, but no potentiation of DOX activities. The arrest at G2/M phase was detected by flow cytometry in both MCF-7 and MCF-7/DOX cells after NAM treatment. Activation of caspase pathway in MCF-7 cells, such as the cleavages of PARP, caspase-6, -7, -9, were observed after exposure to NAM 50 mmol x L(-1), accompanied by the occurrence of chromatin condensation and Annexin V positive cells. However, the cleavages of PARP, caspase-6 and -7 in MCF-7/DOX cells delayed after exposure to NAM for 24 h and obviously increased at 48 h with appearance of chromatin condensation and Annexin V positive cells. SIRT1 deacetylase inhibitors show no cross resistance to MCF-7 drug-resistant cells, and the similar growth-inhibitory actions of them to MCF-7 sensitive and drug-resistant cells by which it is mediated by activation of apoptotic caspase pathway.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Pharmacology
/
Benzamides
/
Breast Neoplasms
/
Doxorubicin
/
Cell Cycle
/
Apoptosis
/
Niacinamide
/
Drug Resistance, Multiple
/
Drug Resistance, Neoplasm
Limits:
Female
/
Humans
Language:
Chinese
Journal:
Acta Pharmaceutica Sinica
Year:
2008
Type:
Article
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