Hypersensitivity of BRCA2 deficient cells to rosemary extract explained by weak PARP inhibitory activity

Abstract Rosemary extract is used in food additives and traditional medicine and has been observed to contain anti-tumor activity. In this study, rosemary extract is hypothesized to induce synthetic lethality in BRCA2 deficient cells by PARP inhibition. Chinese hamster lung V79 cells and its mutant...

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Autores principales:	Cathy Su, Jeffrey P. Gius, Julia Van Steenberg, Alexis H. Haskins, Kazuki Heishima, Chisato Omata, Masahiro Iwayama, Mami Murakami, Takashi Mori, Kohji Maruo, Takamitsu A. Kato
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7565a82dd66f49b1a36dd312937e9dcc
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spelling	oai:doaj.org-article:7565a82dd66f49b1a36dd312937e9dcc2021-12-02T15:05:34ZHypersensitivity of BRCA2 deficient cells to rosemary extract explained by weak PARP inhibitory activity10.1038/s41598-017-16795-32045-2322https://doaj.org/article/7565a82dd66f49b1a36dd312937e9dcc2017-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-16795-3https://doaj.org/toc/2045-2322Abstract Rosemary extract is used in food additives and traditional medicine and has been observed to contain anti-tumor activity. In this study, rosemary extract is hypothesized to induce synthetic lethality in BRCA2 deficient cells by PARP inhibition. Chinese hamster lung V79 cells and its mutant cell lines, V-C8 (BRCA2 deficient) and V-C8 with BRCA2 gene correction were used. Rosemary extract and its major constituent chemicals were tested for their cytotoxicity by colony formation assay in cells of different BRCA2 status. The latter chemicals were tested for inhibitory effect of poly (ADP-ribose) polymerase (PARP) activity in vitro and in vivo. Rosemary has shown selective cytotoxicity against V-C8 cells (IC50 17 µg/ml) compared to V79 cells (IC50 26 µg/ml). Among tested chemicals, gallic acid and carnosic acid showed selective cytotoxicity to V-C8 cells along with PARP inhibitory effects. Carnosol showed comparative PARP inhibitory effects at 100 µM compared to carnosic acid and gallic acid, but the selective cytotoxicity was not observed. In conclusion, we predict that within rosemary extract two specific constituent components; gallic acid and carnosic acid were the cause for the synthetic lethality.Cathy SuJeffrey P. GiusJulia Van SteenbergAlexis H. HaskinsKazuki HeishimaChisato OmataMasahiro IwayamaMami MurakamiTakashi MoriKohji MaruoTakamitsu A. KatoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cathy Su Jeffrey P. Gius Julia Van Steenberg Alexis H. Haskins Kazuki Heishima Chisato Omata Masahiro Iwayama Mami Murakami Takashi Mori Kohji Maruo Takamitsu A. Kato Hypersensitivity of BRCA2 deficient cells to rosemary extract explained by weak PARP inhibitory activity
description	Abstract Rosemary extract is used in food additives and traditional medicine and has been observed to contain anti-tumor activity. In this study, rosemary extract is hypothesized to induce synthetic lethality in BRCA2 deficient cells by PARP inhibition. Chinese hamster lung V79 cells and its mutant cell lines, V-C8 (BRCA2 deficient) and V-C8 with BRCA2 gene correction were used. Rosemary extract and its major constituent chemicals were tested for their cytotoxicity by colony formation assay in cells of different BRCA2 status. The latter chemicals were tested for inhibitory effect of poly (ADP-ribose) polymerase (PARP) activity in vitro and in vivo. Rosemary has shown selective cytotoxicity against V-C8 cells (IC50 17 µg/ml) compared to V79 cells (IC50 26 µg/ml). Among tested chemicals, gallic acid and carnosic acid showed selective cytotoxicity to V-C8 cells along with PARP inhibitory effects. Carnosol showed comparative PARP inhibitory effects at 100 µM compared to carnosic acid and gallic acid, but the selective cytotoxicity was not observed. In conclusion, we predict that within rosemary extract two specific constituent components; gallic acid and carnosic acid were the cause for the synthetic lethality.
format	article
author	Cathy Su Jeffrey P. Gius Julia Van Steenberg Alexis H. Haskins Kazuki Heishima Chisato Omata Masahiro Iwayama Mami Murakami Takashi Mori Kohji Maruo Takamitsu A. Kato
author_facet	Cathy Su Jeffrey P. Gius Julia Van Steenberg Alexis H. Haskins Kazuki Heishima Chisato Omata Masahiro Iwayama Mami Murakami Takashi Mori Kohji Maruo Takamitsu A. Kato
author_sort	Cathy Su
title	Hypersensitivity of BRCA2 deficient cells to rosemary extract explained by weak PARP inhibitory activity
title_short	Hypersensitivity of BRCA2 deficient cells to rosemary extract explained by weak PARP inhibitory activity
title_full	Hypersensitivity of BRCA2 deficient cells to rosemary extract explained by weak PARP inhibitory activity
title_fullStr	Hypersensitivity of BRCA2 deficient cells to rosemary extract explained by weak PARP inhibitory activity
title_full_unstemmed	Hypersensitivity of BRCA2 deficient cells to rosemary extract explained by weak PARP inhibitory activity
title_sort	hypersensitivity of brca2 deficient cells to rosemary extract explained by weak parp inhibitory activity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/7565a82dd66f49b1a36dd312937e9dcc
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_version_	1718388773414240256

Hypersensitivity of BRCA2 deficient cells to rosemary extract explained by weak PARP inhibitory activity

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