title: Predominant enhancement of apoptosis induced by methyl jasmonate in bladder cancer cells: therapeutic effect of the Antp-conjugated Smac peptide.
abstract: Methyl jasmonate (MJ) has recently attracted attention as a promising antitumoral compound because of its highly specific proapoptotic properties in a wide range of malignancies. However, the high doses required to achieve a therapeutic benefit have limited its clinical development. Here, we hypothesize that the family of inhibitor of apoptosis proteins (IAPs) may inhibit MJ-mediated apoptosis in cancer cells. We combined MJ with the IAPs inhibitor, the second mitochondria-derived activator of caspases (Smac) peptide to treat bladder cancer cells. The results showed that the combination of MJ and Smac peptide enhanced the apoptosis-inducing effect in a synergistic manner by releasing and activating IAPs-bounding caspase-3. These findings suggest that the inhibition of IAPs could overcome the resistance of cancer cells to MJ.
authors.affiliation: Department of Urology, Wuhan Union Hospital, Huazhong University of Science and Technology, Hubei Province, China.
authors.forename: Xing-yuan
authors.initials: XY
authors.lastname: Xiao
authors.forename: Guo-song
authors.initials: GS
authors.lastname: Jiang
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Lv
authors.forename: Fu-Qing
authors.initials: FQ
authors.lastname: Zeng
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D051943:Antennapedia Homeodomain Protein; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006690:Bisbenzimidazole; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects*; D003517:Cyclopentanes / Q000494:pharmacology*; D029721:Drosophila Proteins; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D005456:Fluorescent Dyes; D057809:HEK293 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D054883:Oxylipins / Q000494:pharmacology*; D000077022:Survivin; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*
chemical_list: D000085:Acetates; D051943:Antennapedia Homeodomain Protein; D000970:Antineoplastic Agents; C497974:Antp protein, Drosophila; C107489:BIRC5 protein, human; D003517:Cyclopentanes; D029721:Drosophila Proteins; D005456:Fluorescent Dyes; D051034:Inhibitor of Apoptosis Proteins; D009842:Oligopeptides; D054883:Oxylipins; C532637:SMAC peptide; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C072239:methyl jasmonate; D053148:Caspase 3; D053453:Caspase 9; D006690:Bisbenzimidazole