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.
Article
in English
| 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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Neoplastic Stem Cells
/
Paclitaxel
/
Apoptosis
/
Carcinoma, Non-Small-Cell Lung
/
Alpha-Tocopherol
/
Cell Line, Tumor
/
Cell Growth Processes
/
Drug Synergism
/
Drug Therapy, Combination
/
Caspase 8
Limits:
Humans
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2009
Type:
Article
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