Diallyl Disulphide, a Beneficial Component of Garlic Oil, Causes a Redistribution of Cell-Cycle Growth Phases, Induces Apoptosis, and Enhances Butyrate-Induced Apoptosis in Colorectal Adenocarcinoma Cells (HT-29).
Nutr Cancer. 2011 Oct ;63(7):1104-13. Epub 2011 Sep 14. PMID: 21916706
a Molecular Biology Laboratory, Zoology Department, Faculty of Science , Sohag University , Sohag , Egypt.
Colon cancer is a leading and expanding cause of death worldwide. A major contributory factor to this disease is diet composition; some components are beneficial (e.g, dietary fiber), whereas others are detrimental (e.g., alcohol). Garlic oil is a prominent dietary constituent that prevents the development of colorectal cancer. This effect is believed to be mainly due to diallyl disulphide (DADS), which selectively induces redox stress in cancerous (rather than normal) cells that leads to apoptotic cell death. However, the detailed mechanism by which DADS causes apoptosis remains unclear. We show that DADS treatment of colonic adenocarcinoma cells (HT-29) initiates a cascade of molecular events characteristic of apoptosis. These include a decrease in cellular proliferation, translocation of phosphatidylserine to the plasma-membrane outer-layer, activation of caspase-3 and -9, genomic DNA fragmentation, and G(2)/M phase cell-cycle arrest. Short-chain fatty acids (SCFAs), particularly butyrate (abundantly produced in the gut by bacterial fermentation of dietary polysaccharides), enhance colonic cell integrity but, in contrast, inhibit colonic cancer cell growth. Combining DADS with butyrate augmented the apoptotic effect of butyrate on HT-29 cells. These results suggest that the anticancerous properties of DADS afford greater benefit when supplied with other favorable dietary factors (short chain fatty acids/polysaccharides) that likewise reduce colonic tumor development.