Ginsenoside CK induces apoptosis in triple-negative breast cancer cells by targeting glutamine metabolism

Bo Zhang; Rongzhan Fu; Zhiguang Duan; Shihong Shen; Chenhui Zhu; Daidi Fan

doi:10.1016/j.bcp.2022.115101

Ginsenoside CK induces apoptosis in triple-negative breast cancer cells by targeting glutamine metabolism

Biochem Pharmacol. 2022 Aug:202:115101. doi: 10.1016/j.bcp.2022.115101. Epub 2022 May 23.

Authors

Bo Zhang¹, Rongzhan Fu¹, Zhiguang Duan¹, Shihong Shen¹, Chenhui Zhu², Daidi Fan³

Affiliations

¹ Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China; Biotech. & Biomed. Research Institute, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China.
² Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China; Biotech. & Biomed. Research Institute, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China. Electronic address: zch2005@nwu.edu.cn.
³ Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China; Biotech. & Biomed. Research Institute, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China. Electronic address: fandaidi@nwu.edu.cn.

PMID: 35618001
DOI: 10.1016/j.bcp.2022.115101

Abstract

Breast cancer (BC) has replaced lung cancer as the most common cancer worldwide. Ginsenoside CK (CK) can effectively inhibit triple-negative breast cancer (TNBC), the occurrence and development of which are associated with glutamine addiction. However, the connection between CK and glutamine metabolism in TNBC proliferation and the mechanism of cell death induction remains unclear. Here, we found that high glutamine-addicted TNBC cells were particularly sensitive to CK treatment. CK exerted antitumour activity against TNBC by suppressing glutamine consumption and glutamate production via downregulation of glutaminase 1 (GLS1) expression. CK treatment further decreased cellular ATP production, reduced the utilisation of amino acids associated with glutamine metabolism, and induced glutathione (GSH) depletion and reactive oxygen species (ROS) accumulation, consequently triggering apoptosis in TNBC. Furthermore, CK decreased GLS1 expression in SUM159 xenograft mouse mammary tumours and significantly inhibited tumour growth with few side effects. Together, our data provide a powerful theoretical basis for the application of CK as a glutamine metabolic inhibitor in TNBC treatment.

Keywords: Apoptosis; GLS1; Ginsenoside CK; Glutamine metabolism; Triple-negative breast cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis
Cell Line, Tumor
Cell Proliferation
Ginsenosides* / pharmacology
Ginsenosides* / therapeutic use
Glutamine / metabolism
Humans
Mice
Triple Negative Breast Neoplasms* / metabolism

Substances

Ginsenosides
Glutamine
ginsenoside M1