Effects of cyclopalladated compounds on bioenergetics and mitochondrial oxidative state: a study of apoptosis-related mechanisms

Abstract

Cyclopalladated compounds derived from N,N-dimethyl-1-phenethylamine (dmpa) and biphosphine-1,2-bis(diphenylphosphine)ethanebis (dppe) were recently described in the literature as promising agents to cancer therapy because at extremely low concentrations they are able to induce apoptosis in melanoma B16F10-Nex2 cells. However, the complete molecular mechanisms of cyclopalladated-induced apoptosis remain unclear. It is well established the involvement of mitochondria in trigger and/or regulation of apoptosis through of the mitochondrial permeability transition pore with pro-apoptotic proteins releasing to cytosol. Since cyclopalladated-induced apoptosis in tumoral cells seems to involve respiratory collapses, in this work, we will investigate the effects of four cyclopalladated compounds [R(+)Cl dmpa:dppe(1:1); R(+)Cl dmpa:dppe(1:2); S(-)Cl dmpa:dppe(1:1); S(-)Cl dmpa:dppe(1:2)] on the bioenergetics and oxidative state using as model isolated rat liver mitochondria. According to the obtained results in this project, further studies will be performed with mitochondria isolated from tumoral cells in attempt to elucidate the molecular pathways of cyclopalladated induced-apoptosis.