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        TRAIL-induced cell death and caspase-8 activation are inhibited by cisplatin but not carboplatin

        한세준,안태규,최한송,신진나,Sujan Piya,김태형 대한부인종양학회 2009 Journal of Gynecologic Oncology Vol.20 No.2

        Objective: Platinum (Pt) based drugs including cisplatin and carboplatin are widely used as anticancer drugs in various human cancers. Many studies have shown that chemotherapeutic agents synergistically enhance cell death induced by death ligands. However it has been recently reported that cisplatin may inhibit tumor necrosis factorrelated apoptosis-inducing ligand (TRAIL)-induced cell death through inactivation of caspases. Thus, we investigated whether carboplatin also inhibits TRAIL-induced cell death. Methods: HeLa cells were treated with TRAIL in the presence of cisplatin or carboplatin, and cell death was analyzed using the crystal violet staining method. Caspase activation was checked through detection of Bid cleavage by Western blotting using anti-Bid antibody. Results: Cisplatin inhibits TRAIL-induced cell death in HeLa cells; however, carboplatin enhanced TRAIL-induced cell death. Whereas cisplatin inhibited caspase-8-mediated Bid cleavage, carboplatin had no effect on caspase-8 activity. Conclusion: Although cisplatin and carboplatin are platinum-containing cancer therapeutic agents, they have the opposite effects on TRAIL-induced cell death. Objective: Platinum (Pt) based drugs including cisplatin and carboplatin are widely used as anticancer drugs in various human cancers. Many studies have shown that chemotherapeutic agents synergistically enhance cell death induced by death ligands. However it has been recently reported that cisplatin may inhibit tumor necrosis factorrelated apoptosis-inducing ligand (TRAIL)-induced cell death through inactivation of caspases. Thus, we investigated whether carboplatin also inhibits TRAIL-induced cell death. Methods: HeLa cells were treated with TRAIL in the presence of cisplatin or carboplatin, and cell death was analyzed using the crystal violet staining method. Caspase activation was checked through detection of Bid cleavage by Western blotting using anti-Bid antibody. Results: Cisplatin inhibits TRAIL-induced cell death in HeLa cells; however, carboplatin enhanced TRAIL-induced cell death. Whereas cisplatin inhibited caspase-8-mediated Bid cleavage, carboplatin had no effect on caspase-8 activity. Conclusion: Although cisplatin and carboplatin are platinum-containing cancer therapeutic agents, they have the opposite effects on TRAIL-induced cell death.

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