| RRC ID |
77794
|
| 著者 |
Nishimoto K, Okahashi N, Maruyama M, Izumi Y, Nakatani K, Ito Y, Iida J, Bamba T, Matsuda F.
|
| タイトル |
Lipidome and metabolome analyses reveal metabolic alterations associated with MCF-7 apoptosis upon 4-hydroxytamoxifen treatment.
|
| ジャーナル |
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.
|
| 巻・号 |
13(1)
|
| ページ |
18549
|
| 公開日 |
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
|
| リソース情報 |
| ヒト・動物細胞 |
MCF7(RCB1904) |
