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: Jung Ok Ban, Dong Yeon Yuk, Koan Sik Woo, Tae Myoung Kim, Ung Soo Lee, Heon-Sang Jeong, Dae Joong Kim, Yeun Bok Chung, Bang Yeon Hwang, Ki Wan Oh, Jin Tae Hong
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 104 Issue 4 Pg. 374-83 (Aug 2007) ISSN: 1347-8613 [Print] Japan
• PMID: 17721042 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Neoplasm
• NF-kappa B
• Thiophenes
• Tumor Necrosis Factor-alpha
• thiacremonone
• Tetradecanoylphorbol Acetate

Topics

• Apoptosis (drug effects, genetics)
• Blotting, Western
• Cell Line, Tumor
• Cell Survival (drug effects)
• Colonic Neoplasms (genetics, metabolism)
• DNA, Neoplasm (drug effects, metabolism)
• Dose-Response Relationship, Drug
• Electrophoretic Mobility Shift Assay
• Garlic (chemistry)
• Gene Expression Regulation (drug effects)
• Humans
• NF-kappa B (drug effects, genetics, metabolism)
• Tetradecanoylphorbol Acetate
• Thiophenes (administration & dosage, pharmacology)
• Transcription, Genetic (drug effects)
• Tumor Necrosis Factor-alpha (drug effects, metabolism)