Abstract Title:

Genistein sensitizes glioblastoma cells to carbon ions via inhibiting DNA-PKcs phosphorylation and subsequently repressing NHEJ and delaying HR repair pathways.

Abstract Source:

Radiother Oncol. 2018 Apr 20. Epub 2018 Apr 20. PMID: 29685705

Abstract Author(s):

Xiongxiong Liu, Ping Li, Ryoichi Hirayama, Yuzhen Niu, Xinguo Liu, Weiqiang Chen, Xiaodong Jin, Pengcheng Zhang, Fei Ye, Ting Zhao, Bingtao Liu, Qiang Li

Article Affiliation:

Xiongxiong Liu


BACKGROUND AND PURPOSE: Previously, we found genistein could sensitize cancer cells to low linear energy transfer (LET) X-rays via inhibiting DNA-PKcs activities. Especially, high-LET heavy ion produces more DNA double strand breaks (DSBs) than low-LET radiation. Thus, the study was designed to investigate the detailed molecular mechanisms of genistein on sensitizing cancer cells to heavy ions.

MATERIALS AND METHODS: Human glioblastoma (GBM) cell lines with or without genistein pre-treatment were irradiated with high-LET carbon ions. Cell survival was determined with colony formation assay. DNA DSBs were evaluated by means of detectingγ-H2AX foci and immuno-blotting DSB repair proteins, cell apoptosis was detected using Annexin V and PI staining. The interaction of genistein with DNA-PKcs activation site was estimated by molecular docking in the autodock software.

RESULTS: Genistein sensitized DNA-PKcs proficient GBM cells to high-LET carbon ions via delaying the clearance ofγ-H2AX foci. Genistein was physically bound to DNA-PKcs and functionally inhibited the phosphorylation of DNA-PKcs. Consequently, the non-homologous end joining (NHEJ) repair of DSBs was inhibited and the homologous recombination (HR) repair was delayed by genistein, thereby leading to an increasein apoptosis in DNA-PKcs proficient GBM cells after irradiation.

CONCLUSION: Our study demonstrated that genistein holds promise as a radiosensitizer for enhancing the efficacy of carbon ion radiotherapy against DNA-PKcs proficient GBM via inhibiting DNA-PKcs phosphorylation and subsequently repressing NHEJ and delaying HR repair pathways.

Study Type : In Vitro Study
Additional Links
Pharmacological Actions : Radiosensitizer : CK(291) : AC(182)

Print Options

Key Research Topics

Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get Nature's Evidence-Based Pharmacy

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Download Now

500+ pages of Natural Medicine Alternatives and Information.

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2021 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.