title: Cellular Redox Status Regulates Emodin-Induced Radiosensitization of Nasopharyngeal Carcinoma Cells In Vitro and In Vivo.
abstract: Here, we report that regulation of cellular redox status is required for radiosensitization of nasopharyngeal carcinoma (NPC) cells by emodin. We evaluated emodin's radiosensitivity-enhancing ability by using NPC cells in vitro and xenografts in vivo. A clonogenic assay was performed to evaluate NPC cell survival and to determine dose modification factors. Flow cytometry, western blot analysis, and in vivo radiation-induced tumor regrowth delay assays were performed to characterize emodin's effects. Exposure of CNE-1 NPC cells to emodin enhanced their radiosensitivity. HIF-1α expression significantly increased under hypoxic conditions but did not change after treatment with emodin alone. Emodin downregulated mRNA and protein expression of HIF-1α. Cells exposed to radiation and emodin underwent significant cell cycle arrest at the G2/M phase. The percentage of apoptotic cells and reactive oxygen species (ROS) levels were significantly higher in the group exposed to emodin and radiation hypoxic group than in the other groups. Compared to the CNE-1 xenografts exposed to radiation alone, CNE-1 xenografts exposed to radiation with emodin showed significantly enhanced radiation effects. Our data suggest that emodin effectively enhanced the radiosensitivity of CNE-1 cells in vitro and in vivo. The mechanism appears to involve ROS generation and ROS-mediated inhibition of HIF-1α expression.
authors.affiliation: College of Pharmacy, Guangxi Medical University, Nanning 530021, China.
authors.forename: Huaxin
authors.initials: H
authors.lastname: Hou
authors.affiliation: Department of Basic Research, Guangxi Institute for Cancer Research, 71 Hedi Road, Nanning 530021, China.
authors.forename: Danrong
authors.initials: D
authors.lastname: Li
authors.affiliation: College of Pharmacy, Guangxi Medical University, Nanning 530021, China.
authors.forename: Daohai
authors.initials: D
authors.lastname: Cheng
authors.affiliation: Department of Basic Research, Guangxi Institute for Cancer Research, 71 Hedi Road, Nanning 530021, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: College of Pharmacy, Guangxi Medical University, Nanning 530021, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Guangxi Medical University, Nanning 530021, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou