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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Main Authors: Hanan A. Bashmail, Aliaa A. Alamoudi, Abdulwahab Noorwali, Gehan A. Hegazy, Ghada AJabnoor, Hani Choudhry, Ahmed M. Al-Abd
Format: Article
Language:English
Published: Nature Publishing Group 2018-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-018-30046-z
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spelling doaj-fead3b6d3df847a8819eb57af7c0ae382020-12-08T05:57:25ZengNature Publishing GroupScientific Reports2045-23222018-08-018111110.1038/s41598-018-30046-zThymoquinone synergizes gemcitabine anti-breast cancer activity via modulating its apoptotic and autophagic activitiesHanan A. Bashmail0Aliaa A. Alamoudi1Abdulwahab Noorwali2Gehan A. Hegazy3Ghada AJabnoor4Hani Choudhry5Ahmed M. Al-Abd6Departement of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz UniversityDepartement of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz UniversityDepartement of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz UniversityDepartement of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz UniversityDepartement of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz UniversityDepartment of Biochemistry, Faculty of Science, King Abdulaziz UniversityDepartment of Pharmacology, Medical Division, National Research CentreAbstract 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.https://doi.org/10.1038/s41598-018-30046-z
collection DOAJ
language English
format Article
sources DOAJ
author Hanan A. Bashmail
Aliaa A. Alamoudi
Abdulwahab Noorwali
Gehan A. Hegazy
Ghada AJabnoor
Hani Choudhry
Ahmed M. Al-Abd
spellingShingle 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
Scientific Reports
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 Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2018-08-01
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.
url https://doi.org/10.1038/s41598-018-30046-z
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