Solute carrier family 16 member 3 is a target of nodakenetin in breast cancer.

Nodakenetin is a plant-derived coumarin with anti-tumor activities. However, the roles of nodakenetin in treating breast cancer are unknown. This study aimed to investigate the effects of nodakenetin on breast cancer cell viability, apoptosis, and glycolysis, and to explore its action mechanisms. MCF-7 and MDA-MB-468 cell Lines were used in this research. Cell viability was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, and apoptosis was investigated by TdT-mediated dUTP nick-end labeling and flow cytometry assays. Glycolysis was evaluated by determining glucose uptake, lactate production, and adenosine triphosphate (ATP) level. Solute carrier family 16 member 3 (SLC16A3) expression was detected by qRT-PCR and western blotting. The clinical expression of SLC16A3 was analyzed using bioinformatics analysis. We found that nodakenetin reduced the viability and increased apoptosis in breast cancer cells. Nodakenetin suppressed glycolysis in breast cancer cells by decreasing glucose uptake, lactate production, ATP level, and extracellular acidification rate. Moreover, SLC16A3 was identified as a target of nodakenetin and an oncogene in breast cancer. Nodakenetin decreased SLC16A3 expression. SLC16A3 upregulation reversed the effects of nodakenetin on the viability, apoptosis, and glycolysis in breast cancer cells. Additionally, nodakenetin treatment suppressed the growth of breast cancer cells in nude mice. Our findings suggest that nodakenetin inhibits the viability, promotes apoptosis, and represses glycolysis in breast cancer cells through decreasing SLC16A3 expression, proving the anti-cancer potential of nodakenetin in breast cancer.