The fatty acid derivative palmitoylcarnitine abrogates colorectal cancer cell survival by depleting glutathione.

The fatty acid derivative palmitoylcarnitine abrogates colorectal cancer cell survival by depleting glutathione. Am J Physiol Cell Physiol. 2019 Sep 04;: Authors: Turnbull PC, Hughes MC, Perry CGR Abstract Previous evidence suggests that palmitoylcarnitine incubations trigger mitochondrial-mediated apoptosis in HT29 colorectal adenocarcinoma cells, yet non-transformed cells appear resistant. The mechanism by which palmitoylcarnitine induces cancer cell death is unclear. The purpose of this investigation was to examine the relationship between mitochondrial kinetics and glutathione buffering in determining the effect of palmitoylcarnitine on cell survival. HT29 and HCT 116 colorectal adenocarcinoma cells, CCD 841 non-transformed colon cells and MCF7 breast adenocarcinoma cells were exposed to 0μM, 50μM and 100μM palmitoylcarnitine for 24-48 hours. HCT 116 and HT29 cells showed decreased cell survival following palmitoylcarnitine compared to CCD 841 cells. Palmitoylcarnitine stimulated H2O2 emission in HT29 and CCD 841 cells but increased it to a greater level in HT29 cells due largely to a higher basal H2O2 emission. This greater H2O2 emission was associated with lower glutathione buffering capacity and caspase-3 activation in HT29 cells. The glutathione depleting agent, buthionine sulfoximine, sensitized CCD 841 cells and further sensitized HT29 cells to palmitoylcarnitine-induced decreases in cell survival. MCF7 cells did not pro...
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Tags: Am J Physiol Cell Physiol Source Type: research