title: β-Elemene promotes cisplatin-induced cell death in human bladder cancer and other carcinomas.
abstract: Cisplatin-based combination treatment is the most effective systemic chemotherapy for bladder cancer; however, resistance to cisplatin remains a significant problem in the treatment of this disease. β-Elemene is a new natural compound that blocks cell-cycle progression and has a broad spectrum of antitumor activity. This study was conducted to explore the potential of β-elemene as a chemosensitizer for enhancing the therapeutic efficacy and potency of cisplatin in bladder cancer and other solid carcinomas. β-Elemene not only markedly inhibited cell growth and proliferation but also substantially increased cisplatin cytotoxicity towards human bladder cancer 5637 and T-24 cells. Similarly, β-elemene also enhanced cisplatin sensitivity and augmented cisplatin cytotoxicity in small-cell lung cancer and carcinomas of the brain, breast, cervix, ovary, and colorectal tract in vitro, with dose-modifying factors ranging from 5 to 124. β-Elemene-enhanced cisplatin cytotoxicity was associated with increased apoptotic cell death, as determined by DNA fragmentation, and increased activities of caspase-3, -7, -8, -9, and -10 in bladder cancer cell lines. Collectively, these results suggest that β-elemene augments the antitumor activity of cisplatin in human bladder cancer by enhancing the induction of cellular apoptosis via a caspase-dependent mechanism. Cisplatin combined with β-elemene as a chemosensitizer warrants further pre-clinical therapeutic studies and may be useful for the treatment of cisplatin-resistant bladder cancer and other types of carcinomas.
authors.affiliation: Beihai Institute of Endocrine and Metabolic Diseases, Beihai, Guangxi, PR China.
authors.forename: Q Quentin
authors.initials: QQ
authors.lastname: Li
authors.forename: Gangduo
authors.initials: G
authors.lastname: Wang
authors.forename: Huasheng
authors.initials: H
authors.lastname: Liang
authors.forename: Jueli M
authors.initials: JM
authors.lastname: Li
authors.forename: Furong
authors.initials: F
authors.lastname: Huang
authors.forename: Piyush K
authors.initials: PK
authors.lastname: Agarwal
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Zhong
authors.forename: Eddie
authors.initials: E
authors.lastname: Reed
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D012717:Sesquiterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D012717:Sesquiterpenes; C445979:beta-elemene; D053148:Caspase 3; D002945:Cisplatin
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