Reference - Detail
| RRC ID | 77794 |
|---|---|
| Author | Nishimoto K, Okahashi N, Maruyama M, Izumi Y, Nakatani K, Ito Y, Iida J, Bamba T, Matsuda F. |
| Title | Lipidome and metabolome analyses reveal metabolic alterations associated with MCF-7 apoptosis upon 4-hydroxytamoxifen treatment. |
| Journal | Sci Rep |
| Abstract |
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. |
| Volume | 13(1) |
| Pages | 18549 |
| Published | 2023-10-29 |
| DOI | 10.1038/s41598-023-45764-2 |
| PII | 10.1038/s41598-023-45764-2 |
| PMID | 37899460 |
| PMC | PMC10613619 |
| MeSH | Apoptosis Breast Neoplasms* / drug therapy Breast Neoplasms* / metabolism Citrates Female Humans Lipidomics* MCF-7 Cells Metabolome Tamoxifen / pharmacology |
| IF | 3.998 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | MCF7(RCB1904) |