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alpha-Tocopheryl succinate potentiates the paclitaxel-induced apoptosis through enforced caspase 8 activation in human H460 lung cancer cells
Experimental & Molecular Medicine ; : 737-745, 2009.
Artículo en Inglés | WPRIM | ID: wpr-71509
ABSTRACT
Paclitaxel is one of the chemotheraputic drugs widely used for the treatment of nonsmall cell lung cancer (NSCLC) patients. Here, we tested the ability of alpha-tocopheryl succinate (TOS), another promising anticancer agent, to enhance the paclitaxel response in NSCLC cells. We found that sub-apoptotic doses of TOS greatly enhanced paclitaxel-induced growth suppression and apoptosis in the human H460 NSCLC cell lines. Our data revealed that this was accounted for primarily by an augmented cleavage of poly(ADP-ribose) polymerase (PARP) and enhanced activation of caspase-8. Pretreatment with z-VAD-FMK (a pan-caspase inhibitor) or z-IETD-FMK (a caspase-8 inhibitor) blocked TOS/paclitaxel cotreatment-induced PARP cleavage and apoptosis, suggesting that TOS potentiates the paclitaxel-induced apoptosis through enforced caspase 8 activation in H460 cells. Furthermore, the growth suppression effect of TOS/paclitaxel combination on human H460, A549 and H358 NSCLC cell lines were synergistic. Our observations indicate that combination of paclitaxel and TOS may offer a novel therapeutic strategy for improving paclitaxel drug efficacy in NSCLC patient therapy as well as for potentially lowering the toxic side effects of paclitaxel through reduced drug dosage.
Asunto(s)

Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Células Madre Neoplásicas / Paclitaxel / Apoptosis / Carcinoma de Pulmón de Células no Pequeñas / Alfa-Tocoferol / Línea Celular Tumoral / Procesos de Crecimiento Celular / Sinergismo Farmacológico / Quimioterapia Combinada / Caspasa 8 Límite: Humanos Idioma: Inglés Revista: Experimental & Molecular Medicine Año: 2009 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Células Madre Neoplásicas / Paclitaxel / Apoptosis / Carcinoma de Pulmón de Células no Pequeñas / Alfa-Tocoferol / Línea Celular Tumoral / Procesos de Crecimiento Celular / Sinergismo Farmacológico / Quimioterapia Combinada / Caspasa 8 Límite: Humanos Idioma: Inglés Revista: Experimental & Molecular Medicine Año: 2009 Tipo del documento: Artículo