Inhibition of Cell Growth and Induction of Apoptosis via Inactivation of NF-κB by a Sulfurcompound Isolated From Garlic in Human Colon Cancer Cells

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Compounds such as S-allylmercaptocysteine, diallyl disulfide, and S-trityl-<sc>L</sc>-cysteine isolated from garlic have been known to be effective in chemoprevention. Nuclear transcription factor-κB (NF-κB) 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-κB activity and thereby induce apoptotic cell death of colon cancer cells. Treatment with different concentrations (30 – 150 μg/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-α (TNF-α) and tetradeanoyl phorbol acetate (TPA)-induced NF-κB transcriptional and DNA binding activity. Moreover, thiacremonone suppressed NF-κB 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-κB.
社団法人日本薬理学会の論文
2007-08-20