title: Sulforaphane induces reactive oxygen species-mediated mitotic arrest and subsequent apoptosis in human bladder cancer 5637 cells.
abstract: The present study was undertaken to determine whether sulforaphane-derived reactive oxygen species (ROS) might cause growth arrest and apoptosis in human bladder cancer 5637 cells. Our results show that the reduced viability of 5637 cells by sulforaphane is due to mitotic arrest, but not the G2 phase. The sulforaphane-induced mitotic arrest correlated with an induction of cyclin B1 and phosphorylation of Cdk1, as well as a concomitant increased complex between cyclin B1 and Cdk1. Sulforaphane-induced apoptosis was associated with the activation of caspase-8 and -9, the initiators caspases of the extrinsic and intrinsic apoptotic pathways, respectively, and activation of effector caspase-3 and cleavage of poly (ADP-ribose) polymerase. However, blockage of caspase activation inhibited apoptosis and abrogated growth inhibition in sulforaphane-treated 5637 cells. This study further investigated the roles of ROS with respect to mitotic arrest and the apoptotic effect of sulforaphane, and the maximum level of ROS accumulation was observed 3h after sulforaphane treatment. However, a ROS scavenger, N-acetyl-L-cysteine, notably attenuated sulforaphane-mediated apoptosis as well as mitotic arrest. Overall, these results suggest that sulforaphane induces mitotic arrest and apoptosis of 5637 cells via a ROS-dependent pathway.
authors.affiliation: School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea.
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Park
authors.affiliation: Anti-Aging Research Center & Blue-Bio Industry Regional Innovation Center, Dongeui University, Busan 614-714, Republic of Korea.
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Han
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.affiliation: School of Food Science and Technology, Chung-Ang University, Ansung 456-756, Republic of Korea.
authors.forename: Sung-Kwon
authors.initials: SK
authors.lastname: Moon
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju 361-763, Republic of Korea.
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Anti-Aging Research Center & Blue-Bio Industry Regional Innovation Center, Dongeui University, Busan 614-714, Republic of Korea; Department of Food and Nutrition, College of Human Ecology, Dongeui University, Busan 614-714, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Hwang
authors.affiliation: Department of Food and Nutrition, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Kun Young
authors.initials: KY
authors.lastname: Park
authors.affiliation: Anti-Aging Research Center & Blue-Bio Industry Regional Innovation Center, Dongeui University, Busan 614-714, Republic of Korea; Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, Republic of Korea. Electronic address: choiyh@deu.ac.kr.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013454:Sulfoxides; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*
chemical_list: D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D017382:Reactive Oxygen Species; D013454:Sulfoxides; D020169:Caspases; C016766:sulforaphane
keywords: 5637 Cells; Apoptosis; Mitotic arrest; ROS; Sulforaphane