Formosanin C inhibits pulmonary metastasis by targeting stearyl CoA desaturase-1

Shuli Man; Yingfang Cui; Dandan Shi; Panpan Lv; Long Ma; Wenyuan Gao

doi:10.1016/j.phymed.2024.155689

Formosanin C inhibits pulmonary metastasis by targeting stearyl CoA desaturase-1

Phytomedicine. 2024 May 2:129:155689. doi: 10.1016/j.phymed.2024.155689. Online ahead of print.

Authors

Shuli Man¹, Yingfang Cui², Dandan Shi², Panpan Lv², Long Ma², Wenyuan Gao³

Affiliations

¹ State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China. Electronic address: msl@tust.edu.cn.
² State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China.
³ School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin, 300072, China. Electronic address: biochemgao@163.com.

PMID: 38728921
DOI: 10.1016/j.phymed.2024.155689

Abstract

Background: Cisplatin (DDP) as the first-line drug has been used in cancer therapy. However, side effects and drug resistance are the challenges of DDP. Disordered lipid metabolism is related to DDP resistance.

Study design: In this study, formosanin C (FC) as the main compound of Rhizoma Paridis saponins (RPS) inhibits pulmonary metastasis by targeting stearyl CoA desaturase-1.

Methods and results: RPS prolonged the survival period of mice, reduced pulmonary metastases and alleviated colon toxicity caused by DDP. FC as the main compound of RPS enhanced the anti-tumor and anti-metastatic effects of DDP. FC decreased the mRNA level of SCD1 and the content of lipid droplets (LDs) in lung cancer cells. Molecular dynamics and isothermal titration calorimetry verified the binding stability and spontaneously between FC and SCD1. SiSCD1 reduced the content of LDs in cell lines and increased mitochondria (mtROS), which was consistent with the results of FC treatment. The combination group decreased DNA repair associated protein as well as DDP resistance markers such as ERCC1 and 53bp1, and increased DNA damage marker like γH2AX, which indirectly confirmed the occurrence of mtROS. In addition, FC combination with DDP also affected epithelial-mesenchymal transition-related protein like VIM and CDH1 in vivo experiments, and thereby inhibited pulmonary metastasis.

Conclusion: Our research indicated that the FC as the main compound of RPS targeted the CY2 domain of SCD1, inhibited lipid metabolism in mice, and thereby suppressed cancer metastases. This provided support for use of FC to treat cancer based on lipid metabolism pathway.

Keywords: Cisplatin; Formosanin C; Lipids metabolism; Resistance; SCD1.