Cellular and mitochondrial effects of a gold-N Heterocyclic Carbene on LNCaP and PC3 prostate cancer cell lines

Abstract

The discovery of cisplatin and its anti-tumor activities but also its side-effects led to the development of new cytotoxic metal complexes. Metal-based compounds and especially gold N-heterocyclic carbene complexes have shown their antitumoral activities and present a great interest of use in medicine. These metallodrugs have been shown to target nuclear DNA, but also other organelles such as mitochondria. The mechanisms of action have been studied and would involve the triggering of cell death, in particular by apoptosis, highlighting mitochondrial dysfunctions. The organometallic compound used in this study has been characterized by its IC50 and GI50 in two prostatic cancer cell lines (LNCaP and PC3). Its capacity to enter the cells and particularly mitochondria was also analyzed. Furthermore, its effects on several parameters (proliferation, cell death, cell cycle) have been determined in vitro. The compound displayed a cytotoxic effect (IC50 < 5{micro}M) confirmed by the MTT assays and cell death analysis by flow cytometry. It also displayed a cytostatic effect confirmed by the determination of the GI50, and induced a brief cell cycle arrest, depending on the cell line and the metallocarbene concentration. Furthermore, the incubation with the gold N-heterocyclic carbene led to mitochondrial membrane potential changes and decreased the accumulation of the mitochondrial protein Rieske. All our results show a global cytotoxic and cytostatic effects of the gold N-heterocyclic carbene that can involve mitochondria.