Subcellular targets of cisplatin cytotoxicity: An integrated view

Biological evaluation of dimethylpyridine–platinum complexes with potent antiproliferative activity

“…The activation of apoptosis occurs through a mitochondrial membrane potential change and caspase-3 activation 37,38 . Our results support these findings showing that Pt14-Pt16 induces apoptosis in MCF-7 and MDA-MB-231 cells through changing mitochondrial membrane potential.…”

Graphene oxide as a chemosensitizer: Diverted autophagic flux, enhanced nuclear import, elevated necrosis and improved antitumor effects

“…Yet it is known that only z1e5% of intracellular CDDP binds to DNA [36,37] and the remaining 75e85% of CDDP is associated with other molecules such as metallothionein/glutathione [36], microfilaments and proteins [38]. Of note, CDDP can be transported to lysosomes for degradation [39,40] and autophagy may play roles in this delivery route [41,42]. As such, it is tempting to speculate that CDDP-induced autophagy resulted in the CDDP delivery into lysosomes for degradation, which at least partly accounted for the resistance.…”

“…However, lines of evidence have shown that CDDP triggers not only apoptosis but also necrosis [43], especially in cancer cells resistant to chemotherapy drugs [37,44]. The cytotoxic effects of CDDP also arise from both nuclear and cytoplasmic signaling pathways [40]. Although the molecular mechanisms that underlie the cytotoxic potential of cytoplasmic CDDP remain poorly understood, it was likely that the enhanced nuclear import of CDDP altered the distribution of CDDP in the cytosol and nucleus, leading to the switch of death mechanisms.…”

New mechanisms for old drugs: Insights into DNA-unrelated effects of platinum compounds and drug resistance determinants

“…Pt compounds interact with multiple nucleophilic biomolecules, apart from DNA, in different subcellular compartments (Galluzzi et al, 2014a,b;Sancho-Martinez et al, 2012). Although various pumps and transporters have been implicated in influx and cellular distribution of such Pt compounds, the mechanisms of movement of Pt drugs across the plasma membrane remain poorly defined (Howell et al, 2010).…”