PB01 Suppresses Radio-resistance by Regulating ATR Signaling in Human Non-small-cell Lung Cancer Cells

Overview

Journal Sci Rep

Specialty Science

Date 2021 Jun 9

PMID 34103635

Citations 3

Authors

Tae Woo Kim

Da-Won Hong

Sung Hee Hong

Affiliations

Soon will be listed here.

Abstract

Despite the common usage of radiotherapy for the treatment of human non-small-cell lung cancer (NSCLC), cancer therapeutic efficacy and outcome with ionizing radiation remains a challenge. Here, we report the antitumor effects and mechanism of a novel benzothiazole derivative PB01 (4-methoxy-cyclohexane carboxylic acid [2-(3,5-dimethyl-isoxazole-4-yl) sulpanil-benzothiazole-6-yl]-amide) in radiation-resistant human NSCLC cells. PB01 treatment is cytotoxic because it induces reactive oxygen species, ER stress, Bax, cytochrome c expression, the ATR-p53-GADD45ɑ axis, and cleavage of caspase-3 and -9. Additionally, we found that radio-resistant A549 and H460 subclones, named A549R and H460R, respectively, show enhanced epithelial-to-mesenchymal transition (EMT), whereas PB01 treatment inhibits EMT and mediates cell death through ER stress and the ATR axis under radiation exposure in radio-resistant A549R and H460R cells. Together, these results suggest that PB01 treatment can overcome radio-resistance during radiotherapy of NSCLC.

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