2. Academic Validation
  3. Kinsenoside Suppresses DGAT1-Mediated Lipid Droplet Formation to Trigger Ferroptosis in Triple-Negative Breast Cancer

Kinsenoside Suppresses DGAT1-Mediated Lipid Droplet Formation to Trigger Ferroptosis in Triple-Negative Breast Cancer

  • Int J Mol Sci. 2025 Mar 5;26(5):2322. doi: 10.3390/ijms26052322.
Yaqin Yang 1,  Dandan Chen 1,  Yuru Zhu 1,  Min Zhang 1,  Huajun Zhao 1 2
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311402, China.
  • 2 Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
PMID: 40076939 DOI: 10.3390/ijms26052322
Abstract

Triple-negative breast Cancer (TNBC) presents limited therapeutic options and is characterized by a poor prognosis. Although Kinsenoside (KIN) possesses a wide range of pharmacological activities, its effect and mechanism in TNBC remain unclear. The objective of this research was to explore the therapeutic effectiveness and the molecular mechanisms of KIN on TNBC. Xenograft experiment was carried out to assess the impact of KIN on TNBC in vivo. The effect of KIN on TNBC in vitro was evaluated through the analysis of cell cytotoxicity and colony formation assays. Oil Red O staining and BODIPY 493/503 fluorescence staining were employed to detect the effect of KIN on lipid droplet (LD) formation. Transcriptomics and inhibitor-rescue experiments were conducted to investigate the role of KIN on TNBC. Mechanistic experiments, including quantitative real-time polymerase chain reaction (RT-qPCR), Western blotting, diacylglycerol Acyltransferase 1 (DGAT1) overexpression assay, and flow cytometric assay, were employed to uncover the regulatory mechanisms of KIN on TNBC. KIN inhibited tumor growth without causing obvious toxicity to the liver and kidneys. In vitro experiments demonstrated that KIN significantly inhibited the viability and proliferation of TNBC cells, accompanied by decreased LD formation and lipid content. Polyunsaturated fatty acids (PUFAs) levels were significantly increased by KIN. Furthermore, transcriptomics and inhibitor-rescue experiments revealed that KIN induced Ferroptosis in TNBC cells. KIN could significantly regulate ferroptosis-related proteins. Lipid peroxidation, iron accumulation, and GSH depletion also confirmed this. The LD inducer mitigated the KIN-induced Ferroptosis in TNBC. The overexpression of DGAT1 attenuated the effects of KIN on cell viability and proliferation. Furthermore, the overexpression of DGAT1 inhibited the effect of KIN to trigger Ferroptosis in TNBC cells. Our findings confirmed that KIN could trigger Ferroptosis by suppressing DGAT1-mediated LD formation, thereby demonstrating a promising therapeutic effect of KIN in TNBC.

Keywords

DGAT1; ferroptosis; kinsenoside; lipid droplet formation; triple-negative breast cancer.

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