A new 2-pyrone derivative, 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one, synergistically enhances radiation sensitivity in human cervical cancer cells

Abstract

Radiation resistance can be overcome by a combination treatment with chemical modifiers. Here, we showed that treatment with 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one (BHP), a new 2-pyrone derivative, in combination with ionizing radiation enhances the sensitivity of human cervical cancer cells to ionizing radiation through overproduction of reactive oxygen species (ROS). The combined treatment with BHP and ionizing radiation caused a decrease in clonogenic survival and an increase in apoptotic cell death in cervical cancer cells. The combined treatment promoted conformational activation of Bax and led to mitochondrial apoptotic cell death. The combination treatment also induced a marked increase in intracellular ROS level. Inhibition of ROS attenuated the radiosensitizing effect of BHP, concurrent with a decrease in Bax activation, a decrease in mitochondrial cell death, and an increase in clonogenic survival. These results indicate that BHP synergistically enhances sensitivity of human cervical cancer cells to ionizing radiation through elevation of intracellular ROS and that ROS-dependent Bax activation is critically involved in the increase in apoptotic cell death induced by the combined treatment with BHP and ionizing radiation.