Clinically relevant radioresistant cells exhibit resistance to HO by decreasing internal HO and lipid peroxidation

Abstract

Radiation therapy is one of the choices to treat malignant tumors. In radiation therapy, existence of radiation-resistant cell is a major problem to overcome. We established clinically relevant radioresistant cells that had been obtained by exposing to 2 Gy/day X-rays for more than 30 days. These cells are resistant to 2 Gy/day X-ray exposure and anticancer agents. However, the underlying resistance mechanism remains unclear. We investigated the resistance of clinically relevant radioresistant cells to hydrogen peroxide (H 2 O 2 ), confirming a degree of resistance. Neither catalase enzyme activity nor aquaporins appeared to be involved in H 2 O 2 resistance. Mitochondrial DNA copy number, adenosine triphosphate (ATP) concentration, and plasma membrane potential were decreased. The timing of H 2 O 2 intake was delayed and lipid peroxidation was decreased. Sensitivity of clinically relevant radioresistant cells to H 2 O 2 was enhanced by 1-palmitoyl-2-(5′-oxo-valeroyl)-sn-glycero-3-phosphocholine administration. These results suggest that the membrane status is a major factor conferring H 2 O 2 resistance in clinically relevant radioresistant cells, and we should further investigate how membrane status could be used to enhance the therapeutic effect on cancer.