2. Academic Validation
  3. Lipidome and metabolome analyses reveal metabolic alterations associated with MCF-7 apoptosis upon 4-hydroxytamoxifen treatment

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

  • Sci Rep. 2023 Oct 29;13(1):18549. doi: 10.1038/s41598-023-45764-2.
Kazuki Nishimoto 1,  Nobuyuki Okahashi 1 2 3,  Masaharu Maruyama 1,  Yoshihiro Izumi 4,  Kohta Nakatani 4,  Yuki Ito 2 5,  Junko Iida 2 5,  Takeshi Bamba 4,  Fumio Matsuda 6 7 8
Affiliations

Affiliations

  • 1 Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, 1-5 Yamadaoka, Suita, Osaka, 565-0871, Japan.
  • 2 Department of Biotechnology, Osaka University Shimadzu Analytical Innovation Research Laboratory, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, 565-0871, Japan.
  • 3 Industrial Biotechnology Initiative Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, 2-1 Yamadaoka, Suita, 565-0871, Japan.
  • 4 Division of Metabolomics, Medical Research Center for High Depth Omics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
  • 5 Analytical and Measuring Instruments Division, Shimadzu Corporation, 1 Nishinokyo Kuwabara-cho, Nakagyo-ku, Kyoto, 604-8511, Japan.
  • 6 Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, 1-5 Yamadaoka, Suita, Osaka, 565-0871, Japan. [email protected].
  • 7 Department of Biotechnology, Osaka University Shimadzu Analytical Innovation Research Laboratory, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, 565-0871, Japan. [email protected].
  • 8 Industrial Biotechnology Initiative Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, 2-1 Yamadaoka, Suita, 565-0871, Japan. [email protected].
PMID: 37899460 DOI: 10.1038/s41598-023-45764-2
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.

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