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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.
Artículo en Chino | 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.
Asunto(s)
Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Patología / Farmacología / Benzamidas / Neoplasias de la Mama / Doxorrubicina / Ciclo Celular / Apoptosis / Niacinamida / Resistencia a Múltiples Medicamentos / Resistencia a Antineoplásicos Límite: Femenino / Humanos Idioma: Chino Revista: Acta Pharmaceutica Sinica Año: 2008 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Patología / Farmacología / Benzamidas / Neoplasias de la Mama / Doxorrubicina / Ciclo Celular / Apoptosis / Niacinamida / Resistencia a Múltiples Medicamentos / Resistencia a Antineoplásicos Límite: Femenino / Humanos Idioma: Chino Revista: Acta Pharmaceutica Sinica Año: 2008 Tipo del documento: Artículo