Antitumor Activity of Mitochondrial Uncouplers Based on Platinum (II) N-Heterocyclic Carbene Complexes

In the present study, the effects of mitochondrial uncouplers on lung carcinoma cells were investigated. The compounds were found to inhibit cell proliferation by inducing cell cycle arrest at the G1/S transition. Treatment with the tested complexes led to acidification of the extracellular medium, associated with enhanced lactate production due to compensatory increase in glycolytic flux. The effect on HIF signalling has been demonstrated, which is especially intriguing when considering how to overcome neoplastic cells' resistance to chemical agents. Signaling pathway analysis revealed that mitochondrial uncoupling increased ERK1/2 phosphorylation levels, which may represent a compensatory cellular response to energy stress. Exposure to the complexes also resulted in elevated reactive oxygen species (ROS) generation and pronounced morphological alterations. These findings provide further insight into the mechanisms of action of mitochondrial uncouplers and their impact on proliferation, metabolism, and signaling pathways in tumor cells.