α-Tocopheryl succinate potentiates the paclitaxel-induced apoptosis through enforced caspase 8 activation in human H460 lung cancer cells

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 α-tocopheryl succinate (TOS), another promising anticancer agent, to enhance the paclitaxel response in NSCLC cells. We found that sub-apoptotic...

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Bibliographic Details
Published in:Experimental & molecular medicine 2009, 41(10), , pp.737-745
Main Authors: Lim, Soo-Jeong, Choi, Moon Kyung, Kim, Min Jung, Kim, Joo Kyoung
Format: Article
Language:English
Subjects:
alpha-Tocopherol - pharmacology
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Biomedical and Life Sciences
Biomedicine
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Non-Small-Cell Lung - metabolism
Carcinoma, Non-Small-Cell Lung - pathology
Caspase 8 - metabolism
Cell Growth Processes - drug effects
Cell Line, Tumor
Drug Synergism
Drug Therapy, Combination
Humans
Medical Biochemistry
Molecular Medicine
Neoplastic Stem Cells
Original
Paclitaxel - pharmacology
Stem Cells
생화학
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Summary: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 α-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.
ISSN:1226-3613
2092-6413
DOI:10.3858/emm.2009.41.10.080