Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Aged garlic extract potentiates doxorubicin cytotoxicity in human breast cancer cells

Huda Mohammed Alkreathy¹, Noura Farraj AlShehri¹, Fatemah Omer Kamel¹, Ahmed Khalaf Alghamdi³, Ahmed Esmat^1,2, Shahid Karim¹

¹Department of Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; ²Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt; ³College of Medicine- King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia.

For correspondence:- Shahid Karim Email: shahid.karim@yahoo.co.in

Accepted: 15 July 2020 Published: 31 August 2020

Citation: Alkreathy HM, AlShehri NF, Kamel FO, Alghamdi AK, Esmat A, Karim S. Aged garlic extract potentiates doxorubicin cytotoxicity in human breast cancer cells. Trop J Pharm Res 2020; 19(8):1669-1676 doi: 10.4314/tjpr.v19i8.15

© 2020 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the potential chemo-sensitizing effect of aged garlic extract (AGE) on doxorubicin (DOX) in breast cancer cells (MCF-7), and the possible underlying mechanisms.

Methods: Human breast cancer cell line (MCF-7) was treated with AGE and DOX. The cytotoxic effects of AGE and DOX were investigated via cell cycle analysis and apoptosis induction, using flow cytometry. Mechanistic studies involved the determination of cellular uptake of DOX and p-glycoprotein (P-gp) activity.

Results: Combined treatment of MCF7 cells with AGE and DOX produced no significant effect at AGE dose of 10 mg/mL. However, co-treatment with AGE at doses of 50 and 93 mg/mL enhanced the cytotoxicity of DOX on MCF-7 cells, with IC₅₀ values of 0.962 and 0.999 µM, respectively, when compared with 1.85 µM DOX alone. Moreover, Annexin V-FITC and PI techniques showed that AGE significantly increased percentage of cells in late apoptosis. Besides, AGE-DOX treatment significantly increased cellular uptake of DOX and inhibited P-gp activity, when compared with DOX alone (p < 0.05).

Conclusion: AGE enhances the cytotoxic effect of DOX on MCF-7 cells, most likely due to cell cycle distribution, stimulation of apoptosis, increased uptake of DOX by MCF7, and inhibition of P-gp activity.

Keywords: Aged garlic extract, Doxorubicin, Breast cancer, MCF-7 cell line, P-glycoprotein, Apoptosis, Cell cycle