The relationship between cisplatin-induced reactive oxygen species, glutathione, and BCL-2 and resistance to cisplatin.
Cisplatin (cDDP) is an anticancer agent that is widely used in the treatment of many solid tumors. A major obstacle to successful cDDP-based chemotherapy, however, is the intrinsic and acquired resistance of tumor cells to this drug. Greater insight into the molecular mechanisms underlying the modulation of cellular responses to cDDP will aid in the development and optimization of new therapeutic strategies. Apart from induction of DNA damage, recent data have suggested that cDDP also induces the formation of reactive oxygen species that can trigger cell death. Cell death occurs as the result of several simultaneously activated signaling pathways. The specific pathway responsible for cell death depends on the cell type and the treatment conditions. This review focuses on the relationship between glutathione and BCL-2 and their protective role in cDDP-induced reactive oxygen species formation and cDDP resistance.
Brozovic
Anamaria
A
Laboratory for Genotoxic Agents, Division of Molecular Biology, Rudjer Boskovic Institute, Zagreb, Croatia. brozovic@irb.hr
Ambriović-Ristov
Andreja
A
Osmak
Maja
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D005978:Glutathione; D002945:Cisplatin