title: The alkaloid emetine sensitizes ovarian carcinoma cells to cisplatin through downregulation of bcl-xL.
abstract: Cisplatin and its platinum derivatives are first-line chemotherapeutic agents in the treatment of ovarian cancer. However, chemoresistance is the leading cause of therapeutic failure and is responsible for the poor overall survival rate. Here, we describe that emetine, a natural alkaloid used as an anti-amoebiasis drug, sensitized ovarian carcinoma cells to apoptosis induced by cisplatin. The single administration of cisplatin or emetine had a weak effect on cell death. However, co-treatment of cisplatin and emetine remarkably induced apoptosis and reduced the colony formation of ovarian carcinoma cells. Moreover, we showed that apoptosis induced by the combination of cisplatin and emetine was dependent on the activation of caspases -3, -7 and -8. As to the mechanism, downregulation of bcl-xL by emetine was shown to be responsible for enhancing the sensitivity of ovarian cancer cells to cisplatin. These findings suggest that the combination of cisplatin and emetine might be a promising treatment for ovarian cancer.
authors.affiliation: Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Public Health and Environmental Medicine, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Yogosawa
authors.affiliation: Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Iizumi
authors.affiliation: Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakai
authors.affiliation: Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sowa
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D004357:Drug Synergism; D004640:Emetine / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology*; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D051020:bcl-X Protein; D002945:Cisplatin; D004640:Emetine