title: Sulforaphane Induces Cell Death Through G2/M Phase Arrest and Triggers Apoptosis in HCT 116 Human Colon Cancer Cells.
abstract: Sulforaphane (SFN), an isothiocyanate, exists exclusively in cruciferous vegetables, and has been shown to possess potent antitumor and chemopreventive activity. However, there is no available information that shows SFN affecting human colon cancer HCT 116 cells. In the present study, we found that SFN induced cell morphological changes, which were photographed by contrast-phase microscopy, and decreased viability. SFN also induced G2/M phase arrest and cell apoptosis in HCT 116 cells, which were measured with flow cytometric assays. Western blotting indicated that SFN increased Cyclin A, cdk 2, Cyclin B and WEE1, but decreased Cdc 25C, cdk1 protein expressions that led to G2/M phase arrest. Apoptotic cell death was also confirmed by Annexin V/PI and DAPI staining and DNA gel electrophoresis in HCT 116 cells after exposure to SFN. The flow cytometric assay also showed that SFN induced the generation of reactive oxygen species (ROS) and Ca[Formula: see text] and decreased mitochondria membrane potential and increased caspase-8, -9 and -3 activities in HCT 116 cell. Western blotting also showed that SFN induced the release of cytochrome c, and AIF, which was confirmed by confocal microscopy examination. SFN induced ER stress-associated protein expression. Based on those observations, we suggest that SFN may be used as a novel anticancer agent for the treatment of human colon cancer in the future.
authors.affiliation: * Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan.
authors.forename: Kuo-Ching
authors.initials: KC
authors.lastname: Liu
authors.affiliation: * Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan.
authors.forename: Ting-Ying
authors.initials: TY
authors.lastname: Shih
authors.affiliation: † Department of Chinese Medicine Resources, China Medical University, Taichung, Taiwan.
authors.forename: Chao-Lin
authors.initials: CL
authors.lastname: Kuo
authors.affiliation: ∥ School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, Taiwan.|** Department of Chinese Medicine, E-Da Hospital, Kaohsiung, Taiwan.
authors.forename: Yi-Shih
authors.initials: YS
authors.lastname: Ma
authors.affiliation: † Department of Chinese Medicine Resources, China Medical University, Taichung, Taiwan.
authors.forename: Jiun-Long
authors.initials: JL
authors.lastname: Yang
authors.affiliation: ‡ School of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Wu
authors.affiliation: § Department of Physiology, China Medical University, Taichung, Taiwan.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Huang
authors.affiliation: †† Department of Surgery, China Medical University Beigang Hospital, Yunlin, Taiwan.|‡‡ School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Kuang-Chi
authors.initials: KC
authors.lastname: Lai
authors.affiliation: ¶ Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.|§§ Department of Biotechnology, Asia University, Wufeng, Taichung, Taiwan.
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D017304:Annexin A5 / Q000235:genetics / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects* / Q000235:genetics; D002455:Cell Division / Q000187:drug effects* / Q000235:genetics; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D016195:G2 Phase / Q000187:drug effects* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D017879:Isothiocyanates / Q000737:chemistry*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013268:Stimulation, Chemical; D013454:Sulfoxides
chemical_list: D017304:Annexin A5; D000972:Antineoplastic Agents, Phytogenic; D018797:Cell Cycle Proteins; D017879:Isothiocyanates; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D013454:Sulfoxides; D020169:Caspases; C016766:sulforaphane; D002118:Calcium
keywords: Apoptosis; Endoplasm Reticulum Stress; G2/M Arrest; HCT116 Colon Cancer Cells; Mitochondria; Sulforaphane