Abstract. Cis-diamminedichloroplatinum (II) cisplatin (CDDP) is an organometallic compound frequently used in anti-cancer therapy, in particular ovarian, testicular, and head and neck tumors. We found cisplatin was effective against human promyelocytic leukemia cell line HL-60, inhibiting cell cycle progression and inducing time-and concentrationdependent cell death. Presence of nuclear fragmentation, caspase-3 cleavage and annexin V positivity suggests cell death occurred by apoptosis, although DNA internucleosomal fragmentation was not detected. In addition, analysis of malondialdehyde (MDA) production and protein carbonylation indicated that cisplatin increased lipid peroxidation and oxidation of cell proteins. This occurrence was prevented by antioxidants such as N-acetylcysteine (N-aC) and glutathione (GSH), which, consistently, were also able to prevent CDDPinduced cell death. Collectively, these findings indicate that, besides growth inhibition, an increase of oxygen radicals and lipid degradation can account for a significant part of CDDPinduced apoptosis.
The objective of the present study was to investigate the biochemical mechanisms underlying gentamicin cytotoxicity in OC-k3 cells derived from an immortalized cell line developed from the organ of Corti of transgenic mice. Administration of 50 µM gentamicin significantly reduced cell proliferation and viability, as well as initiating morphological changes associated with apoptosis. Protein kinase C (PKC) α activity was increased in gentamicin-treated cells, peaking 15 min after dosing (+138.2%). This PKCα increase was followed by a rise of glutathione (GSH) efflux and a concomitant 29% decrease in intracellular GSH levels at 30 min. PKCα-specific inhibitors blocked these cytotoxic effects. Gentamicin also increased malondialdehyde levels, while N-acetylcysteine, GSH and ascorbic acid prevented gentamicin-induced cell death. These findings suggest that gentamicin cytotoxicity involves a production of intracellular reactive oxygen species and a concomitant PKC-dependent fall of intracellular scavenging abilities (GSH), events that together drive cells to undergo apoptosis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.