Lipidome and metabolome analyses reveal metabolic alterations associated with MCF-7 apoptosis upon 4-hydroxytamoxifen treatment

• Published in: Scientific reports Vol. 13; no. 1; p. 18549
• Main Authors: Nishimoto, Kazuki, Okahashi, Nobuyuki, Maruyama, Masaharu, Izumi, Yoshihiro, Nakatani, Kohta, Ito, Yuki, Iida, Junko, Bamba, Takeshi, Matsuda, Fumio
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.10.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/45/320; 631/45/608; Antitumor agents; Apoptosis; Breast cancer; Cell death; Diacylglycerol O-acyltransferase; Diglycerides; Electron transport; Gene expression; Humanities and Social Sciences; Lipid metabolism; Lipids; Membrane potential; Metabolism; Metabolomics; Mortality; multidisciplinary; Science; Science (multidisciplinary); Tumor cell lines
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-45764-2

4-hydroxytamoxifen (OHT) is an anti-cancer drug that induces apoptosis in breast cancer cells. Although changes in lipid levels and mitochondrial respiration have been observed in OHT-treated cells, the overall mechanisms underlying these metabolic alterations are poorly understood. In this study, time-series metabolomics and lipidomics were used to analyze the changes in metabolic profiles induced by OHT treatment in the MCF-7 human breast cancer cell line. Lipidomic and metabolomic analyses revealed increases in ceramide, diacylglycerol and triacylglycerol, and decreases in citrate, respectively. Gene expression analyses revealed increased expression of ATP-dependent citrate lyase (ACLY) and subsequent fatty acid biosynthetic enzymes, suggesting that OHT-treated MCF-7 cells activate citrate-to-lipid metabolism. The significance of the observed metabolic changes was evaluated by co-treating MCF-7 cells with OHT and ACLY or a diacylglycerol O -acyltransferase 1 (DGAT1) inhibitor. Co-treatment ameliorated cell death and reduced mitochondrial membrane potential compared to that in OHT treatment alone. The inhibition of cell death by co-treatment with an ACLY inhibitor has been observed in other breast cancer cell lines. These results suggest that citrate-to-lipid metabolism is critical for OHT-induced cell death in breast cancer cell lines.