The relationship between cisplatin-induced reactive oxygen species, glutathione, and BCL-2 and resistance to cisplatin

Abstract

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.

Keywords::

• BCL-2
• cisplatin
• drug resistance
• glutathione
• ROS

Acknowledgements

The authors would like to thank Prof. Dr. Gerhard Fritz for critical reading of the manuscript.

Declaration of interest

This study was supported by funds of the Ministry of Science, Education and Sport of the Republic of Croatia (Projects No. 098-0982913-2748 and No. 098-0982913-2850). The authors state no conflict of interest.