Activation of surrogate death receptor signaling triggers peroxynitrite-dependent execution of cisplatin-resistant cancer cells.

ABSTRACT: Platinum-based drugs remain as the cornerstone of cancer chemotherapy; however, development of multidrug resistance presents a therapeutic challenge. This study aims at understanding the molecular mechanisms underlying resistance to cisplatin and unraveling surrogate signaling networks that could revert sensitivity to apoptosis stimuli. We made use of three different sets of cell lines, A549 and H2030 non-small-cell lung cancer (NSCLC) and A2780 ovarian cancer cells and their cisplatin-resistant variants. Here we report that cisplatin-resistant cell lines displayed a multidrug-resistant phenotype. Changes in mitochondrial metabolism and defective mitochondrial signaling were unraveled in the resistant cells. More interestingly, a marked increase in sensitivity of the resistant cells to dea

SUBMITTER: Seah S 

PROVIDER: S-EPMC4632318 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature