Thymoquinone synergizes gemcitabine anti-breast cancer activity via modulating its apoptotic and autophagic activities

Abstract The use of anti-cancer adjuvant therapy is rationalized by potentiating the efficacy, and/or protecting from major side effects of chemotherapeutics. Thymoquinone (TQ) is a naturally occurring compound with cumulative evidence of anti-cancer properties. In this study, we assessed the chemom...

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Autores principales:	Hanan A. Bashmail, Aliaa A. Alamoudi, Abdulwahab Noorwali, Gehan A. Hegazy, Ghada AJabnoor, Hani Choudhry, Ahmed M. Al-Abd
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fead3b6d3df847a8819eb57af7c0ae38
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spelling	oai:doaj.org-article:fead3b6d3df847a8819eb57af7c0ae382021-12-02T15:08:28ZThymoquinone synergizes gemcitabine anti-breast cancer activity via modulating its apoptotic and autophagic activities10.1038/s41598-018-30046-z2045-2322https://doaj.org/article/fead3b6d3df847a8819eb57af7c0ae382018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-30046-zhttps://doaj.org/toc/2045-2322Abstract The use of anti-cancer adjuvant therapy is rationalized by potentiating the efficacy, and/or protecting from major side effects of chemotherapeutics. Thymoquinone (TQ) is a naturally occurring compound with cumulative evidence of anti-cancer properties. In this study, we assessed the chemomodulatory potential of TQ to gemcitabine (GCB) against human breast adenocarcinoma (MCF-7), and ductal carcinoma (T47D) cells. TQ showed cytotoxic effects against MCF-7 and T47D with IC50’s of 64.9 ± 14 µM and 165 ± 2 µM, respectively. The IC50’s of GCB against MCF-7 and T47D were 0.9 ± 0.18 µM and 14.3 ± 2.8 µM and were significantly reduced after combination with TQ to 0.058 ± 12 µM and 2.3 ± 0.2 µM, respectively. The CI- values were indicative of synergism in MCF-7 and T47D cells (0.15 and 0.30, respectively). Further investigation showed that GCB caused significant anti-proliferative effect reflected by increasing cell population in S-phase in both cell lines. TQ potentiated GCB-induced anti-proliferative activity in both cell lines. GCB induced considerable apoptosis in T47D cell line, and TQ significantly increased GCB-induced apoptotic effects by 1.5 to 3.6 folds. Interestingly, GCB, TQ and their combination induced significant autophagic cell death in the apoptosis defected MCF-7 cells. In addition, TQ, GCB and their combination depleted breast cancer associated stem cell (CD44(+)/CD24(−)/(low)) clone within MCF-7 and T47D cells by 3.8% to 27.5%. In conclusion, TQ showed promising chemomodulatory effects to GCB against breast cancer cells via inducing apoptosis, necrosis and autophagy, in addition to depleting tumor associated resistant stem cell fraction.Hanan A. BashmailAliaa A. AlamoudiAbdulwahab NoorwaliGehan A. HegazyGhada AJabnoorHani ChoudhryAhmed M. Al-AbdNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hanan A. Bashmail Aliaa A. Alamoudi Abdulwahab Noorwali Gehan A. Hegazy Ghada AJabnoor Hani Choudhry Ahmed M. Al-Abd Thymoquinone synergizes gemcitabine anti-breast cancer activity via modulating its apoptotic and autophagic activities
description	Abstract The use of anti-cancer adjuvant therapy is rationalized by potentiating the efficacy, and/or protecting from major side effects of chemotherapeutics. Thymoquinone (TQ) is a naturally occurring compound with cumulative evidence of anti-cancer properties. In this study, we assessed the chemomodulatory potential of TQ to gemcitabine (GCB) against human breast adenocarcinoma (MCF-7), and ductal carcinoma (T47D) cells. TQ showed cytotoxic effects against MCF-7 and T47D with IC50’s of 64.9 ± 14 µM and 165 ± 2 µM, respectively. The IC50’s of GCB against MCF-7 and T47D were 0.9 ± 0.18 µM and 14.3 ± 2.8 µM and were significantly reduced after combination with TQ to 0.058 ± 12 µM and 2.3 ± 0.2 µM, respectively. The CI- values were indicative of synergism in MCF-7 and T47D cells (0.15 and 0.30, respectively). Further investigation showed that GCB caused significant anti-proliferative effect reflected by increasing cell population in S-phase in both cell lines. TQ potentiated GCB-induced anti-proliferative activity in both cell lines. GCB induced considerable apoptosis in T47D cell line, and TQ significantly increased GCB-induced apoptotic effects by 1.5 to 3.6 folds. Interestingly, GCB, TQ and their combination induced significant autophagic cell death in the apoptosis defected MCF-7 cells. In addition, TQ, GCB and their combination depleted breast cancer associated stem cell (CD44(+)/CD24(−)/(low)) clone within MCF-7 and T47D cells by 3.8% to 27.5%. In conclusion, TQ showed promising chemomodulatory effects to GCB against breast cancer cells via inducing apoptosis, necrosis and autophagy, in addition to depleting tumor associated resistant stem cell fraction.
format	article
author	Hanan A. Bashmail Aliaa A. Alamoudi Abdulwahab Noorwali Gehan A. Hegazy Ghada AJabnoor Hani Choudhry Ahmed M. Al-Abd
author_facet	Hanan A. Bashmail Aliaa A. Alamoudi Abdulwahab Noorwali Gehan A. Hegazy Ghada AJabnoor Hani Choudhry Ahmed M. Al-Abd
author_sort	Hanan A. Bashmail
title	Thymoquinone synergizes gemcitabine anti-breast cancer activity via modulating its apoptotic and autophagic activities
title_short	Thymoquinone synergizes gemcitabine anti-breast cancer activity via modulating its apoptotic and autophagic activities
title_full	Thymoquinone synergizes gemcitabine anti-breast cancer activity via modulating its apoptotic and autophagic activities
title_fullStr	Thymoquinone synergizes gemcitabine anti-breast cancer activity via modulating its apoptotic and autophagic activities
title_full_unstemmed	Thymoquinone synergizes gemcitabine anti-breast cancer activity via modulating its apoptotic and autophagic activities
title_sort	thymoquinone synergizes gemcitabine anti-breast cancer activity via modulating its apoptotic and autophagic activities
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/fead3b6d3df847a8819eb57af7c0ae38
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Thymoquinone synergizes gemcitabine anti-breast cancer activity via modulating its apoptotic and autophagic activities

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