Cisplatin and the curcuminoid, EF24, modulate distinct apoptosis pathways in ovarian cancer, auditory and renal cell lines

ABSTRACT: Abstract Purpose To determine whether the curcuminoid (3E,5E)-3,5-bis[(2-fluorophenyl) methylene]-4-piperidinone (EF24) increases the anti-cancer effects of cisplatin against the human ovarian cancer cell line, A2780, and the cisplatin resistant human ovarian cancer line, A2780cis, and to determine whether EF24 prevents cisplatin-mediated side effects in the mouse auditory hybridoma cell line, HEI-OC1, and the human kidney cell line, HEK-293T. Methods The effect of cisplatin and EF24 on cellular viability was measured using the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Reactive oxygen species (ROS) production was measured using flow cytometry. The expression and activity of apoptosis signal transduction proteins (apoptosis inducing factor [AIF], caspases-3/7, -8, -9 and -12) was measured using western blots and luminescence assays. Results Cisplatin, EF24 and combination treatments caused similar reductions in cell viability (IC50 range: 0.83-7.35). Cisplatin and combination treatments increased ROS production in A2780 and A2780cis cells, and decreased ROS levels in HEI-OC1 cells. Caspase-9 may modulate caspase-3/7 activity in A2780 cells, and EF24 might potentiate cisplatin’s effect and act through caspases-8 and -9 in A2780cis cells. EF24 reduced caspase activity in HEI-OC1 cells; the other treatments increased activity. ROS production and caspase-3/7 activity was unchanged in HEK-293T cells. The treatments did not alter AIF and caspase-12 expression in all cell lines. Conclusion Cisplatin and EF24 may act through distinct cell death mechanisms in some cancer and non-cancer cells. However, our data suggests that combining these two compounds does not promote anti-cancer synergies, or prevent toxicity in non-cancer cell lines.

SUBMITTER: Michael E. Smith 

PROVIDER: S-BSST311 | biostudies-other |

REPOSITORIES: biostudies-other