title: Molecular mechanism of diallyl disulfide in cell cycle arrest and apoptosis in HCT-116 colon cancer cells.
abstract: Diallyl disulfide (DADS) is the most prevalent oil-soluble sulfur compound in garlic and inhibits cell proliferation in many cancer cell lines. Here we examined DADS cytotoxicity in a redox-mediated process, involving reactive oxygen species (ROS) production. In the present study, p53-independent cell cycle arrest at G2/M phase was observed with DADS treatment, along with time-dependent increase of cyclin B1. In addition, apoptosis was also observed upon 24-h DADS treatment accompanied by activation of p53. In HCT-116 cells, DADS application induced a dose-dependent increase and time-dependent changes in ROS production. Scavenging of DADS-induced ROS by N-acetyl cysteine or reduced glutathione inhibited cell cycle arrest, apoptosis and p53 activation by DADS. These results suggest that ROS trigger the DADS-induced cell cycle arrest and apoptosis and that ROS are involved in stress-induced signaling upstream of p53 activation. Transfection of p53 small interfering RNA prevents the accumulation of cleaved poly(ADP-ribose) polymerase and sub-G1 cell population by 65% and 35%, respectively. Moreover, DADS-induced apoptosis was also prevented by treatment with oligomycin, which is known to prevent p53-dependent apoptosis by reducing ROS levels in mitochondria. These results suggest that mitochondrial ROS may serve as second messengers in DADS-induced apoptosis, which requires activation of p53.
authors.affiliation: Department of Microbiology and Immunology, Pusan National University School of Medicine, Busan, Republic of Korea.
authors.forename: Ju-Dong
authors.initials: JD
authors.lastname: Song
authors.forename: Sang Kwon
authors.initials: SK
authors.lastname: Lee
authors.forename: Kang Mi
authors.initials: KM
authors.lastname: Kim
authors.forename: Si Eun
authors.initials: SE
authors.lastname: Park
authors.forename: Sung-Joo
authors.initials: SJ
authors.lastname: Park
authors.forename: Koan Hoi
authors.initials: KH
authors.lastname: Kim
authors.forename: Soon Cheol
authors.initials: SC
authors.lastname: Ahn
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Park
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D004220:Disulfides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D045325:HCT116 Cells; D006801:Humans; D009840:Oligomycins / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000498:Allyl Compounds; D000975:Antioxidants; C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D004220:Disulfides; D009840:Oligomycins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C028009:diallyl disulfide; D011065:Poly(ADP-ribose) Polymerases; D016203:CDC2 Protein Kinase