AN N-terminal Smac peptide sensitizes human prostate carcinoma cells to methyl jasmonate-induced apoptosis.
Although the anti-cancer agent methyl jasmonate (MJ) has been shown to selectively target malignant cells while sparing normal ones, hormone-refractory prostate cancer cells are relatively resistant to MJ than other cancer cells. In the present study, we investigated the effect of cell permeable seven-residue peptide of Smac (SmacN7), an antagonist of the inhibitor of apoptosis proteins (IAPs), on MJ-induced apoptosis. SmacN7 significantly enhanced the growth inhibition effect of MJ in human prostate cancer cells, but not in proximal tubular epithelial cells. Moreover, SmacN7 sensitizes MJ-induced apoptosis through both caspase-9-dependent and -independent pathways. Thus, blockade of the over-expressed IAPs in cancer cells could yield a potential therapeutic benefit in jasmonates-based chemotherapy.
Department of Urology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
Guosong
G
Jiang
Jun
J
Zhao
Xingyuan
X
Xiao
Dan
D
Tao
Chaohui
C
Gu
Qiangsong
Q
Tong
Binfeng
B
Luo
Liang
L
Wang
Fuqing
F
Zeng
D000085:Acetates / Q000494:pharmacology*; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003517:Cyclopentanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D054883:Oxylipins / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
D000085:Acetates; D003517:Cyclopentanes; D051034:Inhibitor of Apoptosis Proteins; D009842:Oligopeptides; D054883:Oxylipins; C532637:SMAC peptide; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C072239:methyl jasmonate; D053148:Caspase 3; D053453:Caspase 9