Targeting reactive oxygen species to overcome cisplatin resistance in lung cancer

Medhi  Wangpaichitr; George  Theodoropoulos; Niramol  Savaraj

Authors

Medhi Wangpaichitr Department of Veterans Affairs, Research Service, Miami, FL 33125 and Department of Surgery, Surgical Oncology, University of Miami, Miami. FL 33136
George Theodoropoulos Department of Veterans Affairs, Research Service, Miami, FL 33125
Niramol Savaraj Department of Veterans Affairs, Research Service, Miami, FL 33125 and Department of Medicine, Hematology/Oncology, University of Miami, Miami, FL 33136

Keywords:

lung cancer, cisplatin resistance, reactive oxygen species

Abstract

Cisplatin resistance remains a major problem in the treatment of both small cell and non small cell lung cancer (NSCLC). We have discovered that cisplatin resistant (CR) cells share one common biochemical parameter, increased reactive oxygen species (ROS), when compared to normal cells and their parental cells counterparts. Treating CR cells with either a ROS inducing agent (elesclomol), or an antioxidant agent (N-acetylcysteine) resulted in a significant growth inhibitory effect. This suggested that ROS levels were an important component in the survival of these cells. Co-treatment of cisplatin with NAC however resulted in and antagonistic effect, while elesclomol in combination with cisplatin treatment enhanced cisplatin sensitivity in CR cells. Our findings suggest a novel approach to overcome CR in lung tumors. Combining a ROS inducing agent with cisplatin may prove to be clinically efficacious.

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