WEE1 Inhibition Enhances Sensitivity to Hypoxia/reoxygenation in HeLa Cells

Overview

Journal J Radiat Res

Publisher Oxford University Press

Specialties Environmental Health
Oncology
Radiology

Date 2019 Jul 27

PMID 31347653

Citations 2

Authors

Tatsuaki Goto

Hisao Homma

Atsushi Kaida

Masahiko Miura

Affiliations

Soon will be listed here.

Abstract

Hypoxia/reoxygenation (H/R) treatment reportedly induces DNA damage response (DDR), including DNA double-strand break (DSB) repair and G2 arrest, resulting in reduction of clonogenic survival. Because WEE1 plays a key role in the G2/M checkpoint along with CHK1/2, we investigated the effect of WEE1 inhibition on H/R-induced DDR using HeLa cells. The H/R treatment combined with WEE1 inhibitor abrogated G2 arrest, subsequently leading to the cells entering the M phase, and finally resulting in mitotic catastrophe after prolonged mitosis. Colony-forming assay showed an enhanced decrease in the surviving fraction and the focus formation of BRCA1 was significantly reduced. We demonstrate for the first time that WEE1 inhibition enhances H/R-induced cell death accompanied by mitotic catastrophe and that the process may be mediated by homologous recombination.

Citing Articles

WEE1 Inhibitor Adavosertib Exerts Antitumor Effects on Colorectal Cancer, Especially in Cases with Mutations.

Ariyoshi M, Yuge R, Kitadai Y, Shimizu D, Miyamoto R, Yamashita K Cancers (Basel). 2024; 16(18).

PMID: 39335109 PMC: 11429655. DOI: 10.3390/cancers16183136.

Fluctuation in radioresponse of HeLa cells during the cell cycle evaluated based on micronucleus frequency.

Shimono H, Kaida A, Homma H, Nojima H, Onozato Y, Harada H Sci Rep. 2020; 10(1):20873.

PMID: 33257719 PMC: 7705701. DOI: 10.1038/s41598-020-77969-0.

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