title: Escin induces apoptosis in human renal cancer cells through G2/M arrest and reactive oxygen species-modulated mitochondrial pathways.
abstract: Escin, a natural pentacyclic triterpenoid compound, exhibits antitumor effects on various types of human cancer cells, but its effect on human renal cancer cells has not been fully elucidated. In the present study, we demonstrated that escin elicits cytotoxic effects on human renal cancer cells (786-O and Caki-1) in a dose-dependent manner, as determined by MTT assay. Escin induced G2/M arrest, and then increased the sub-G1 population, Annexin V binding, activation of caspase-9/-3, cleavage of poly(ADP-ribose) polymerase (PARP) and Bax protein. Escin also decreased the anti-apoptotic protein levels of Bcl-2, X-linked inhibitor of apoptosis protein and survivin. In addition, escin induced reactive oxygen species (ROS) generation, leading to mitochondrial membrane potential dysfunction and inducing apoptosis in 786-O renal cancer cells, which were suppressed by antioxidants, such as NAC. Collectively, our results suggest that escin induces apoptosis via the intrinsic-mitochondrial apoptosis pathway through G2/M arrest and ROS generation in human renal cancer cells. Escin appears to have potential as a clinically useful chemotherapeutic agent for human renal cancer.
authors.affiliation: Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan, R.O.C.
authors.forename: Sheau-Yun
authors.initials: SY
authors.lastname: Yuan
authors.affiliation: Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan, R.O.C.
authors.forename: Chen-Li
authors.initials: CL
authors.lastname: Cheng
authors.affiliation: Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan, R.O.C.
authors.forename: Shian-Shiang
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan, R.O.C.
authors.forename: Hao-Chung
authors.initials: HC
authors.lastname: Ho
authors.affiliation: Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan, R.O.C.
authors.forename: Kun-Yuan
authors.initials: KY
authors.lastname: Chiu
authors.affiliation: Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan, R.O.C.
authors.forename: Chuan-Shu
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan, R.O.C.
authors.forename: Cheng-Che
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Nursing, Hung Kuang University, Taichung 43302, Taiwan, R.O.C.
authors.forename: Ming-Yuh
authors.initials: MY
authors.lastname: Shiau
authors.affiliation: Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan, R.O.C.
authors.forename: Yen-Chuan
authors.initials: YC
authors.lastname: Ou
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D004928:Escin / Q000494:pharmacology*; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D004928:Escin; D020169:Caspases