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

• 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
• ISSN: 1226-3613; 2092-6413
• DOI: 10.3858/emm.2009.41.10.080

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.