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4 February 2020 Genistein Enhances Radiosensitivity of Human Hepatocellular Carcinoma Cells by Inducing G2/M Arrest and Apoptosis
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Abstract

New radiosensitizers are urgently needed for radiation therapy patients with localized hepatocellular carcinoma (HCC) that is refractory to radical surgery. We previously found that genistein, a major soy isoflavone, exerts radioprotective effects on L-02 normal liver cells at low concentrations. Here, we report that 5 µM genistein shows less harm to L-02 cells than HCC cells and that it significantly enhances the radiosensitivity of HCC cells by enhancing DNA damage, chromosomal aberrations and cell cycle arrest at G2/M phase and by exacerbating apoptosis. Mechanistically, genistein aggravates X-ray-induced decreases in the levels of phospho-Bad (Ser136) but enhances the levels of phospho-Chk2 (Thr68), phospho-ATM (Ser1981) and γ-H2AX. Micro-array analysis indicated that downregulation of POU6F and CCNE2 expression and upregulation of FBXO32 and cyclin B1 expression might play vital roles in genistein-induced radiosensitivity. These findings suggest genistein as an interesting candidate for adjuvant radiotherapy for HCC and indicate that genistein causes less harm to normal cells than HCC cells by inducing G2/M arrest and apoptosis.

©2020 by Radiation Research Society. All rights of reproduction in any form reserved.
Hongli Yan, Jing Jiang, Aiying Du, Jinli Gao, Daisong Zhang, and Lihua Song "Genistein Enhances Radiosensitivity of Human Hepatocellular Carcinoma Cells by Inducing G2/M Arrest and Apoptosis," Radiation Research 193(3), 286-300, (4 February 2020). https://doi.org/10.1667/RR15380.1
Received: 11 March 2019; Accepted: 10 January 2020; Published: 4 February 2020
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