title: Diallyl sulfide promotes cell-cycle arrest through the p53 expression and triggers induction of apoptosis via caspase- and mitochondria-dependent signaling pathways in human cervical cancer Ca Ski cells.
abstract: Diallyl sulfide (DAS) is a component of garlic (Alliaceae family). Although diallyl polysulfide has been shown to exhibit anticancer activities, no report explored DAS-affected cell death in human cervical cancer cells in vitro. This study investigated DAS affected on cell-cycle regulation and apoptosis in human cervical cancer Ca Ski cells. DAS at 25-100 μM decreased the viability of Ca Ski cells by increasing G0/G1 phase arrest followed by induction of apoptosis in concentration- and time-dependent effects. Flow cytomteric assay indicated that DAS (75 μM) promoted the production of Ca(2+) accumulation and decreased the level of mitochondrial membrane potential in Ca Ski cells. Western blotting showed that 75 μM of DAS-induced G0/G1 phase arrest was mediated through the increased expression of p21, p27, and p53 with a simultaneous decrease in CDK2, CDK6, and CHK2 expression. The characteristics of apoptosis, such as morphological changes and DNA condensation, altered the ratio of Bax/Bcl-2 and sub-G1 phase occurred in Ca Ski cells after exposure to DAS. Furthermore, DAS induced mitochondrial dysfunction, leading to the release of cytochrome c for causing apoptosis in Ca Ski cells. These findings suggest that DAS might be a potential chemotherapeutic agent for the treatment of cervical cancer.
authors.affiliation: Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Tsan-Hung
authors.initials: TH
authors.lastname: Chiu
authors.forename: Kai-Ying
authors.initials: KY
authors.lastname: Lan
authors.forename: Mei-Due
authors.initials: MD
authors.lastname: Yang
authors.forename: Jen-Jyh
authors.initials: JJ
authors.lastname: Lin
authors.forename: Te-Chun
authors.initials: TC
authors.lastname: Hsia
authors.forename: Chin-Tung
authors.initials: CT
authors.lastname: Wu
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
authors.forename: Fu-Shin
authors.initials: FS
authors.lastname: Chueh
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000502:physiology; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013440:Sulfides / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D000498:Allyl Compounds; D017382:Reactive Oxygen Species; D013440:Sulfides; D016159:Tumor Suppressor Protein p53; C038491:allyl sulfide; D020169:Caspases