Screen identifies fasudil as a radioprotector on human fibroblasts.

Yao, Y; Chen, C; Cai, Z; Liu, G; Ding, C; Lim, D; Chao, D; Feng, Z

Screen identifies fasudil as a radioprotector on human fibroblasts.

Yao, Y Chen, C Cai, Z Liu, G Ding, C Lim, D Chao, D Feng, Z

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Publisher:: OXFORD UNIV PRESS
Publication Type:: Journal Article
Citation:: Toxicol Res (Camb), 2022, 11, (4), pp. 662-672
Issue Date:: 2022-08

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Field	Value	Language
dc.contributor.author	Yao, Y
dc.contributor.author	Chen, C
dc.contributor.author	Cai, Z
dc.contributor.author	Liu, G
dc.contributor.author	Ding, C
dc.contributor.author	Lim, D
dc.contributor.author	Chao, D
dc.contributor.author	Feng, Z
dc.date.accessioned	2023-10-09T01:44:59Z
dc.date.available	2022-06-27
dc.date.available	2023-10-09T01:44:59Z
dc.date.issued	2022-08
dc.identifier.citation	Toxicol Res (Camb), 2022, 11, (4), pp. 662-672
dc.identifier.issn	2045-452X
dc.identifier.issn	2045-4538
dc.identifier.uri	http://hdl.handle.net/10453/172578
dc.description.abstract	BACKGROUND: Radioprotectors safeguard biological system exposed to ionizing radiation (IR) by protecting normal cells from radiation damage during radiotherapy. Due to the toxicity and limited clinical utility of the present radioprotectors, it prompts us to identify novel radioprotectors that could alleviate IR-induced cytotoxicity of normal tissues. AIMS AND METHODS: To identify new radioprotectors, we screened a chemical molecular library comprising 253 compounds in normal human fibroblasts (HFs) or 16HBE cells upon IR by CCK-8 assays and clonogenic survival assays. Fasudil was identified as a potential effective radioprotector. RESULTS: The results indicated that Fasudil exerts radioprotective effects on HFs against IR-induced DNA double-strand breaks (DSBs) through the regulation of DSB repair. Fasudil increased homologous recombination (HR) repair by 45.24% and decreased non-homologous end-joining (NHEJ) by 63.88% compared with untreated cells, without affecting changes to cell cycle profile. We further found that fasudil significantly facilitated the expression and foci formation of HR core proteins such as Rad51 and BRCA1 upon IR, and decreased the expression of NHEJ-associated proteins such as DNA-PKcs at 24 h post-IR. CONCLUSION: Our study identified fasudil as a novel radioprotector that exert radioprotective effects on normal cells through regulation of DSB repair by promoting HR repair.
dc.format	Electronic-eCollection
dc.language	eng
dc.publisher	OXFORD UNIV PRESS
dc.relation.ispartof	Toxicol Res (Camb)
dc.relation.isbasedon	10.1093/toxres/tfac042
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	0399 Other Chemical Sciences, 1115 Pharmacology and Pharmaceutical Sciences
dc.subject.classification	3214 Pharmacology and pharmaceutical sciences
dc.title	Screen identifies fasudil as a radioprotector on human fibroblasts.
dc.type	Journal Article
utslib.citation.volume	11
utslib.location.activity	England
utslib.for	0399 Other Chemical Sciences
utslib.for	1115 Pharmacology and Pharmaceutical Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/IMPACCT
utslib.copyright.status	closed_access	*
dc.date.updated	2023-10-09T01:44:55Z
pubs.issue	4
pubs.publication-status	Published online
pubs.volume	11
utslib.citation.issue	4

Abstract:

BACKGROUND: Radioprotectors safeguard biological system exposed to ionizing radiation (IR) by protecting normal cells from radiation damage during radiotherapy. Due to the toxicity and limited clinical utility of the present radioprotectors, it prompts us to identify novel radioprotectors that could alleviate IR-induced cytotoxicity of normal tissues. AIMS AND METHODS: To identify new radioprotectors, we screened a chemical molecular library comprising 253 compounds in normal human fibroblasts (HFs) or 16HBE cells upon IR by CCK-8 assays and clonogenic survival assays. Fasudil was identified as a potential effective radioprotector. RESULTS: The results indicated that Fasudil exerts radioprotective effects on HFs against IR-induced DNA double-strand breaks (DSBs) through the regulation of DSB repair. Fasudil increased homologous recombination (HR) repair by 45.24% and decreased non-homologous end-joining (NHEJ) by 63.88% compared with untreated cells, without affecting changes to cell cycle profile. We further found that fasudil significantly facilitated the expression and foci formation of HR core proteins such as Rad51 and BRCA1 upon IR, and decreased the expression of NHEJ-associated proteins such as DNA-PKcs at 24 h post-IR. CONCLUSION: Our study identified fasudil as a novel radioprotector that exert radioprotective effects on normal cells through regulation of DSB repair by promoting HR repair.

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http://hdl.handle.net/10453/172578