Inhibition of cell growth and induction of apoptosis via inactivation of NF-κB 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-kappa B (NF-kappa B) 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-kappa B activity and thereby induce apoptotic cell death of colon cancer cells. Treatment with different concentrations (30-150 mu g/ml) of thiacremonone for various periods (0-48 h) inhibited colon cancer cell (SW620 and HCT 116) growth followed by induction of apoptosis in a dose-dependent manner. We also found that thiacremonone modulated tumor necrosis factor-a (TNF-alpha) and tetradeanoyl phorbol acetate (TPA)-induced NF-kappa B transcriptional and DNA binding activity. Moreover, thiacremonone suppressed NF-kappa B 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-kappa B.