alpha-Tocopheryl succinate potentiates the paclitaxel-induced apoptosis through enforced caspase 8 activation in human H460 lung cancer cells.
10.3858/emm.2009.41.10.080
- Author:
Soo Jeong LIM
1
;
Moon Kyung CHOI
;
Min Jung KIM
;
Joo Kyoung KIM
Author Information
1. Department of Bioscience and Biotechnology, Sejong University, Seoul 143-747, Korea. sjlim@sejong.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
apoptosis;
carcinoma, non-small-cell lung;
caspase 8;
paclitaxel;
alpha-tocopherol
- MeSH:
Antineoplastic Agents/*pharmacology;
Apoptosis/*drug effects;
Carcinoma, Non-Small-Cell Lung/*drug therapy/metabolism/pathology;
Caspase 8/metabolism;
Cell Growth Processes/drug effects;
Cell Line, Tumor;
Drug Synergism;
Drug Therapy, Combination;
Humans;
Neoplastic Stem Cells;
Paclitaxel/pharmacology;
alpha-Tocopherol/*pharmacology
- From:Experimental & Molecular Medicine
2009;41(10):737-745
- CountryRepublic of Korea
- Language:English
-
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.
