title: Diallyl sulfide induces cell cycle arrest and apoptosis in HeLa human cervical cancer cells through the p53, caspase- and mitochondria-dependent pathways.
abstract: Diallyl sulfide (DAS), one of the main active constituents of garlic, causes growth inhibition of cancer cells in vitro and promotes immune responses in vivo in experimental settings. However, its effects on the induction of cell cycle and apoptosis in human cervical cancer cells are still unclear. The aims of this study were to explore the anti-cancer effects of DAS in HeLa human cervical cancer cells and to investigate the underlying mechanisms in vitro. Cytotoxicity and apoptosis in HeLa human cervical cancer cells were examined by the morphological changes, viability assay, 4',6-Diamidino-2-phenylindole dihydrochloride (DAPI) staining, comet assay, Western blotting and confocal microscopy examination. The results showed that DAS treatment for 24-72 h resulted in a marked decrease in cell viability time- and dose-dependently. Flow cytometric analysis showed that a 48-h treatment of 75 µM DAS induced G0/G1 cell cycle arrest and sub-G1 phase (apoptosis) in HeLa cells. Typical apoptotic nucleus alterations were observed by fluorescence microscopy in HeLa cells after exposure to DAS using DAPI staining. Cells treated with different concentrations of DAS also showed changes typical of apoptosis such as morphological changes, DNA damage and fragmentation, dysfunction of mitochondria, cytochrome c release and increased expression of pro-caspase-3 and -9. DAS also promoted the release of AIF and Endo G from mitochondria in HeLa cells. In conclusion, DAS induced G0/G1 cell cycle arrest and apoptosis in HeLa cells through caspase- and mitochondria and p53 pathways providing further understanding of the molecular mechanisms of DAS action in cervical cancer. This study, therefore, revealed that DAS significantly inhibits the growth and induces apoptosis of human cervical cancer HeLa cells in vitro.
authors.affiliation: School of Pharmacy, China Medical University, Taichung 404, Taiwan, ROC.
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Wu
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Chung
authors.forename: Kuo-Ching
authors.initials: KC
authors.lastname: Liu
authors.forename: Rick Sai-Chuen
authors.initials: RS
authors.lastname: Wu
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
authors.forename: Nou-Ying
authors.initials: NY
authors.lastname: Tang
authors.forename: Chyi
authors.initials: C
authors.lastname: Lo
authors.forename: Te-Chun
authors.initials: TC
authors.lastname: Hsia
authors.forename: Chien-Chih
authors.initials: CC
authors.lastname: Yu
authors.forename: Fu-Shin
authors.initials: FS
authors.lastname: Chueh
authors.forename: Song-Shei
authors.initials: SS
authors.lastname: Lin
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D014176:Protein Biosynthesis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D013440:Sulfides / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000498:Allyl Compounds; D000975:Antioxidants; D013440:Sulfides; D016159:Tumor Suppressor Protein p53; C038491:allyl sulfide; D020169:Caspases