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Hydroxycitric acid potentiates the cytotoxic effect of tamoxifen in MCF-7 breast cancer cells through inhibition of ATP citrate lyase.

Authors
  • Ismail, Ahmed1
  • Doghish, Ahmed S2
  • E M Elsadek, Bakheet3
  • Salama, Salama A4
  • Mariee, Amr D5
  • 1 Biochemistry Department, Faculty of Pharmacy, Al-Azhar University, P.O. Box 11231, Nasr City, Cairo, Egypt. Electronic address: [email protected] , (Egypt)
  • 2 Biochemistry Department, Faculty of Pharmacy, Al-Azhar University, P.O. Box 11231, Nasr City, Cairo, Egypt; Biochemistry Department, Faculty of Pharmacy, Badr University in Cairo, Badr City, Cairo, Egypt. , (Egypt)
  • 3 Biochemistry Department, Faculty of Pharmacy, Al-Azhar University, Assuit Branch, P.O. Box 71524, Assuit, Egypt. , (Egypt)
  • 4 Pharmacology and Toxicology Department, Faculty of Pharmacy, Al-Azhar University, P.O. Box 11231, Nasr City, Cairo, Egypt. , (Egypt)
  • 5 Biochemistry Department, Faculty of Pharmacy, Al-Azhar University, P.O. Box 11231, Nasr City, Cairo, Egypt. , (Egypt)
Type
Published Article
Journal
Steroids
Publication Date
Aug 01, 2020
Volume
160
Pages
108656–108656
Identifiers
DOI: 10.1016/j.steroids.2020.108656
PMID: 32439410
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Hydroxycitric acid (HCA), a dietary-derived weight loss supplement, competitively inhibits ATP citrate lyase (ACLY). Tamoxifen (TAM) is the most frequently used therapy for estrogen receptor (ER)-positive breast cancer patients, but its application was restricted due to efficacy related issues. Lipid metabolic reprogramming plays a key role in cancer progression and response to treatment. This study will test the hypothesis that targeting lipid metabolic enzymes could enhance TAM effect against breast cancer cells. MCF-7 ER-positive breast cancer cell line was used, and the cytotoxic effect of TAM treatment, alone and in combination with HCA was evaluated. Flowcytometric analysis of apoptosis following TAM and/or HCA treatment was additionally performed. Besides, the effects of TAM and/or HCA on ACLY, acetyl CoA carboxylase alpha (ACC-α) and fatty acid synthase (FAS) expression were investigated. Likewise, expression of ER-α protein through TAM and/or HCA treatment was examined. Cell contents of cholesterol and triglyceride were quantified. Treatment with TAM or HCA significantly reduced cell viability in a concentration-dependent manner whereas co-treatment synergistically reduced cell viability, promoted apoptosis, and decreased the expression of ACLY, ACC-α, and FAS. Intracellular triglyceride and cholesterol were accumulated in response to treatment with TAM and/or HCA. Moreover, either solitary TAM or TAM/ HCA co-treatment increased ER-α protein levels non significantly. Our results revealed that TAM effects on breast cancer are mediated, in part, through the regulation of key genes involved in lipid metabolism. Accordingly, inhibition of ACLY by HCA might be beneficial to enhance the therapeutic index of TAM against breast cancer. Copyright © 2020 Elsevier Inc. All rights reserved.

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