PB01 suppresses radio-resistance by regulating ATR signaling in human non-small-cell lung cancer cells

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-methox...

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Autores principales:	Tae Woo Kim, Da-Won Hong, Sung Hee Hong
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5f51feb4025944279304412ca9ff5d38
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spelling	oai:doaj.org-article:5f51feb4025944279304412ca9ff5d382021-12-02T17:52:42ZPB01 suppresses radio-resistance by regulating ATR signaling in human non-small-cell lung cancer cells10.1038/s41598-021-91716-z2045-2322https://doaj.org/article/5f51feb4025944279304412ca9ff5d382021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91716-zhttps://doaj.org/toc/2045-2322Abstract 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.Tae Woo KimDa-Won HongSung Hee HongNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tae Woo Kim Da-Won Hong Sung Hee Hong PB01 suppresses radio-resistance by regulating ATR signaling in human non-small-cell lung cancer cells
description	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.
format	article
author	Tae Woo Kim Da-Won Hong Sung Hee Hong
author_facet	Tae Woo Kim Da-Won Hong Sung Hee Hong
author_sort	Tae Woo Kim
title	PB01 suppresses radio-resistance by regulating ATR signaling in human non-small-cell lung cancer cells
title_short	PB01 suppresses radio-resistance by regulating ATR signaling in human non-small-cell lung cancer cells
title_full	PB01 suppresses radio-resistance by regulating ATR signaling in human non-small-cell lung cancer cells
title_fullStr	PB01 suppresses radio-resistance by regulating ATR signaling in human non-small-cell lung cancer cells
title_full_unstemmed	PB01 suppresses radio-resistance by regulating ATR signaling in human non-small-cell lung cancer cells
title_sort	pb01 suppresses radio-resistance by regulating atr signaling in human non-small-cell lung cancer cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5f51feb4025944279304412ca9ff5d38
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PB01 suppresses radio-resistance by regulating ATR signaling in human non-small-cell lung cancer cells

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