Inhibition of cell growth and induction of apoptosis via inactivation of NF-kappaB by a sulfurcompound isolated from garlic in human colon cancer cells.
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.
Ban
Jung Ok
JO
College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk, Korea.
Yuk
Dong Yeon
DY
Woo
Koan Sik
KS
Kim
Tae Myoung
TM
Lee
Ung Soo
US
Jeong
Heon-Sang
HS
Kim
Dae Joong
DJ
Chung
Yeun Bok
YB
Hwang
Bang Yeon
BY
Oh
Ki Wan
KW
Hong
Jin Tae
JT
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
D004273:DNA, Neoplasm; D016328:NF-kappa B; D013876:Thiophenes; D014409:Tumor Necrosis Factor-alpha; C524083:thiacremonone; D013755:Tetradecanoylphorbol Acetate