Sodium butyrate sensitizes human colon adenocarcinoma COLO 205 cells to both intrinsic and TNF-α-dependent extrinsic apoptosis |
| |
Authors: | Beata Pajak Barbara Gajkowska Arkadiusz Orzechowski |
| |
Institution: | (1) Department of Cell Ultrastructure, Mossakowski Medical Research Center, Polish Academy of Sciences, Pawinskiego 5, 02-106 Warsaw, Poland;(2) Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences (SGGW), Nowoursynowska 159, 02-776 Warsaw, Poland |
| |
Abstract: | Overexpression of cFLIP protein seems to be critical in the antiapoptotic mechanism of immune escape of human COLO 205 colon
adenocarcinoma cells. Actually, cFLIP appears to inhibit the death receptor ligand-mediated cell death. Application of the
metabolic inhibitor sodium butyrate (NaBt), short-chain volatile fatty acid, sensitized COLO 205 cells to TNF-α-mediated apoptosis.
Western-blot analysis revealed that the susceptibility of human COLO 205 cells to apoptogenic stimuli resulted from time-dependent
reduction in cFLIP and simultaneous up-regulation of TNF-R1 protein levels. Additionally, the combined TNF-α and NaBt treatment
caused cleavage of Bid and caspase-9 activation, as well as cytochrome c release from mitochondria. Thus, the evidence of this study indicates that NaBt facilitates the death receptor signal evoked
by TNF-α. Moreover, NaBt alone initiated intrinsic apoptosis, that in turn was abolished by intracellular BCL-2 delivery.
It confirms the involvement of mitochondria in the proapoptotic activity of NaBt. The activation of mitochondrial pathway
was substantiated by up-regulated expression of BAK with concomitant reduction of antiapoptotic BCL-xL, XIAP and survivin proteins. These findings suggest that NaBt could represent a good candidate for the new therapeutic strategy
aimed to improve chemo- and immunotherapy of colon cancer. |
| |
Keywords: | TNF-α Sodium butyrate cFLIP Intrinsic apoptosis Immune escape Colon cancer |
本文献已被 SpringerLink 等数据库收录! |
|