3-Bromopyruvate potentiates TRAIL-induced apoptosis in human colon cancer cells through a reactive oxygen species- and caspase-dependent mitochondrial pathway.

This study aimed to investigate the inhibitory effect of co-treatment of 3-Bromopyruvate (3-BP) as a potent anticancer agent with TRAIL on colon cancer cells (HT-29). The results of present study indicated that combined treatment with 3-BP and TRAIL inhibited the proliferation of HT-29 cells to a greater extent (88.4%) compared with 3-BP (54%) or TRAIL (11%) treatment alone. In contrast, the combination of 3-BP and TRAIL had no significant inhibitory effect on the proliferation of normal cells (HEK-293) (8.4%). At a cellular mechanistic level, the present study showed that 3-BP sensitized human colon cancer cells to TRAIL-induced apoptosis via ROS generation, upregulation of Bax, downregulation of Bcl-2 and survivin, release of cytochrome c into the cytosol and activation of caspase3. In normal cells, 3-BP, TRAIL or combination of both had no significant effect on the ROS levels, release of cytochrome c and caspase3 activity. Therefore, the combination of 3-BP and TRAIL can be a promising therapeutic strategy for treatment of colon cancer. PMID: 31491344 [PubMed - as supplied by publisher]
Source: Canadian Journal of Physiology and Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Can J Physiol Pharmacol Source Type: research