We have shown previously that garlic constituent
diallyl trisulfide (DATS) inhibits growth of cultured and xenografted human
prostate cancer cells in association with apoptosis induction, but the mechanism of cell death is not fully understood. The present study systematically investigates the role of inhibitor of apoptosis (IAP) family
proteins in the regulation of DATS-induced apoptosis using cultured PC-3 and LNCaP human
prostate cancer cells and dorsolateral prostate from control and DATS-treated transgenic
adenocarcinoma of mouse prostate (TRAMP) mice. Level of X-linked inhibitor of apoptosis (
XIAP) protein was decreased on 8-hour treatment with 20 and 40 μmol/L DATS, but this effect was partially attenuated at the 16-hour time point. DATS-mediated decline in
XIAP protein level was partially reversible in the presence of proteasomal inhibitor
MG132. In contrast, DATS-treated PC-3 and LNCaP cells exhibited marked induction of
survivin and cellular
inhibitor of apoptosis protein 1 (cIAP1)
proteins. Induction of
survivin protein expression resulting from DATS exposure was associated with an increase in its
mRNA level. Dorsolateral prostates from DATS-treated TRAMP mice exhibited statistically significant downregulation of XIAP and induction of
survivin protein compared with those of control mice. Ectopic expression of XIAP conferred partial but significant protection against DATS-induced apoptosis. On the other hand, DATS-induced apoptosis was only marginally affected by RNA interference of
survivin or cIAP1. In conclusion, the present study indicates that the DATS-induced apoptosis in
prostate cancer cells is mediated in part by suppression of
XIAP protein expression, and that XIAP represents a viable
biomarker of DATS response for future clinical investigations.