Diallyl disulfide, from garlic oil, synthesizes human colonic adenocarcinoma cell line (Caco-2) to TNF-alpha-mediated apoptosis through up-regulation of membrane FAS levels
Mohammed O. Altonsy1, Hala I Madkour2, Reda S Yousef 3 and Simon C. Andrews,4
1Molecular Biology Lab., Zoology Department, Faculty of Science, Sohag University, Egypt.
2Pharmacology Department, Faculty of Medicine, Sohag University, Egypt.
3Biochemistry Department, Faculty of Medicine, Sohag University, Egypt.
4The School of Biological Sciences, University of Reading, Reading, UK.
Abstract: Colon cancer cells resistance to apoptosis inducing factors, particularly those working through the extrinsic apoptotic rout, such as Tumour necrosis factor alpha (TNF-α), may due to that these cells lack of the presence of FAS receptor on their membrane, to which TNF-α binds and causes the recruitment of caspase-8 and other caspases cascade required in apoptotic cell death. In addition to its reported impact as anti-tumour dietary elements, Diallyl disulfide (DADS), a major organosulfur compound found in garlic oil, was examined in this research for its ability to induce membrane FAS expression in colonic adenocarcinoma cell line (Caco-2), and thereby synthetizes such cells to TNF-alpha-mediated apoptosis. Our results show that the administration of DADS to Caco-2 cell cultures significantly increased the number of dead cells, exhibited morphological changes characteristic to apoptosis and induced caspas-3 cleavage but not caspase-8. Western blot along with flow-cytometry data confirmed the induction of FAS expression, at the protein level, after DADS treatment, RT-PCR also confirmed FAS expression, at the transcriptional level. This resulted in restoring Caco-2 cells sensitivity to TNF-α and initiating the extrinsic pathway through FAS and caspase-8 cleavage. These results suggest that DADS induces apoptosis in colonic cancerous cells not only through the intrinsic pathways but also through enhancing the extrinsic pathway.
[Mohammed O. Altonsy, Hala I Madkour, Reda S Yousef and Simon C. Andrews Diallyl disulfide, from garlic oil, synthesizes human colonic adenocarcinoma cell line (Caco-2) to TNF-alpha-mediated apoptosis through up-regulation of membrane FAS levels. J Am Sci 2013;9(3):173-180] (ISSN: 1545-1003). http://www.jofamericanscience.org. 22
Key words: Diallyl disulfide, garlic oil, colonic adenocarcinoma, TNF-alpha, apoptosis and FAS.