title: Inhibition of cell growth and induction of apoptosis via inactivation of NF-kappaB by a sulfurcompound isolated from garlic in human colon cancer cells.
abstract: Compounds such as S-allylmercaptocysteine, diallyl disulfide, and S-trityl-L-cysteine isolated from garlic have been known to be effective in chemoprevention. Nuclear transcription factor-kappaB (NF-kappaB) has been known to be an implicated factor in apoptotic cell death of several cancer cells. In this study, we investigated whether a sulfurcompound (named thiacremonone) isolated from garlic could modulate NF-kappaB activity and thereby induce apoptotic cell death of colon cancer cells. Treatment with different concentrations (30 - 150 microg/ml) of thiacremonone for various periods (0 - 48 h) inhibited colon cancer cell (SW620 and HCT116) growth followed by induction of apoptosis in a dose-dependent manner. We also found that thiacremonone modulated tumor necrosis factor-alpha (TNF-alpha) and tetradeanoyl phorbol acetate (TPA)-induced NF-kappaB transcriptional and DNA binding activity. Moreover, thiacremonone suppressed NF-kappaB target anti-apoptotic genes (Bcl-2, cIAP1/2, and XIAP) and inflammatory genes (iNOS and COX-2), whereas it induced apoptotic genes (Bax, cleaved caspse-3, and cleaved PARP) expression. These results suggest that a novel sulfurocompound from garlic inhibited colon cancer cell growth through induction of apoptotic cell death by modulating of NF-kappaB.
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk, Korea.
authors.forename: Jung Ok
authors.initials: JO
authors.lastname: Ban
authors.forename: Dong Yeon
authors.initials: DY
authors.lastname: Yuk
authors.forename: Koan Sik
authors.initials: KS
authors.lastname: Woo
authors.forename: Tae Myoung
authors.initials: TM
authors.lastname: Kim
authors.forename: Ung Soo
authors.initials: US
authors.lastname: Lee
authors.forename: Heon-Sang
authors.initials: HS
authors.lastname: Jeong
authors.forename: Dae Joong
authors.initials: DJ
authors.lastname: Kim
authors.forename: Yeun Bok
authors.initials: YB
authors.lastname: Chung
authors.forename: Bang Yeon
authors.initials: BY
authors.lastname: Hwang
authors.forename: Ki Wan
authors.initials: KW
authors.lastname: Oh
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D005737:Garlic / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D016328:NF-kappa B / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; D016328:NF-kappa B; D013876:Thiophenes; D014409:Tumor Necrosis Factor-alpha; C524083:thiacremonone; D013755:Tetradecanoylphorbol Acetate