Hydroxycitric acid potentiates the cytotoxic effect of tamoxifen in MCF-7 breast cancer cells through inhibition of ATP citrate lyase
| Autor: | Salama A. Salama, Amr D. Mariee, Bakheet E. M. Elsadek, Ahmed Ismail, Ahmed S. Doghish |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Antineoplastic Agents
Hormonal ATP citrate lyase Cell Survival Clinical Biochemistry Estrogen receptor Apoptosis Breast Neoplasms 030209 endocrinology & metabolism Biochemistry Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology stomatognathic system medicine Humans Citrates Viability assay Enzyme Inhibitors skin and connective tissue diseases Molecular Biology Cell Proliferation Pharmacology Dose-Response Relationship Drug Molecular Structure Chemistry Organic Chemistry Cancer medicine.disease Hydroxycitric acid Tamoxifen MCF-7 030220 oncology & carcinogenesis ATP Citrate (pro-S)-Lyase MCF-7 Cells Cancer research Drug Screening Assays Antitumor hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Steroids. 160:108656 |
| ISSN: | 0039-128X |
| DOI: | 10.1016/j.steroids.2020.108656 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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