Tangeretin boosts the anticancer activity of metformin in breast cancer cells via curbing the energy production.

Autor: Mdkhana B; Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates; College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates., Zaher DM; Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates; College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates., Abdin SM; Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates; College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates., Omar HA; Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates; College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62511 Egypt. Electronic address: hanyomar@sharjah.ac.ae.
Jazyk: angličtina
Zdroj: Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2021 Mar; Vol. 83, pp. 153470. Date of Electronic Publication: 2021 Jan 17.
DOI: 10.1016/j.phymed.2021.153470
Abstrakt: Background: Breast cancer is the first leading cause of women cancer-related deaths worldwide. While there are many proposed treatments for breast cancer, low efficacy, toxicity, and resistance are still major therapeutic obstacles. Thus, there is a need for safer and more effective therapeutic approaches. Because of the direct link between obesity and carcinogenesis, energy restriction mimetic agents (ERMAs) such as the antidiabetic agent, metformin was proposed as a novel antiproliferative agent. However, the anticancer dose of metformin alone is relatively high and impractical to be implemented safely in patients. The current work aimed to sensitize resistant breast cancer cells to metformin's antiproliferative effect using the natural potential anticancer agent, tangeretin.
Methods: The possible synergistic combination between metformin and tangeretin was initially evaluated using MTT cell viability assay in different breast cancer cell lines (MCF-7, MDA-MB-231, and their resistant phenotype). The possible mechanisms of synergy were investigated via Western blotting analysis, reactive oxygen species (ROS) measurement, annexin/PI assay, cell cycle analysis, and wound healing assay.
Results: The results indicated the ability of tangeretin to improve the anticancer activity of metformin. Interestingly, the improved activity was almost equally observed in both parental and resistant cancer cells, which underlines the importance of this combination in cases of the emergence of resistance. The synergy was mediated through the enhanced activation of AMPK and ROS generation in addition to the improved inhibition of cell migration, induction of cell cycle arrest, and apoptosis in cancer cells.
Conclusion: The current work underscores the importance of metformin as an ERMA in tackling breast cancer and as a novel approach to boost its anticancer activity via a synergistic combination with tangeretin.
(Copyright © 2021. Published by Elsevier GmbH.)
Databáze: MEDLINE
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