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


CONCLUSIONS
Although cisplatin and carboplatin are platinum-containing cancer therapeutic agents, they have the opposite effects on TRAIL-induced cell death.
Han
Sei-Jun
SJ
Department of Obstetrics and Gynecology, Chosun University School of Medicine, Gwangju, Korea.
Ahn
Tae-Kyu
TK
Choi
Han-Song
HS
Shin
Jin-Na
JN
Piya
Sujan
S
Kim
Tae-Hyoung
TH