Aerial Parts of Selaginella doederleinii Hieron as an Anticancer Agent against Luminal A Breast Cancer (T47D) Cell Line

Luminal A is the most widely diagnosed breast cancer subtype worldwide. The existing luminal A therapy faces some challenges, such as drug resistance and toxicity. Therefore, new therapeutic approaches are urgently required. The application of medicinal plants, particularly aerial parts of Selaginella doederleinii Hieron, becomes an attempting strategy due to its abundant bioactive compounds that can target numerous signaling pathways. Therefore, this research aimed to investigate the anticancer potential and mechanism of S. doederleinii extract and fractions on luminal A breast cancer (T47D) cells. WST-1 assay was used to examine the cytotoxicity of the ethanolic extract and several fractions of S. doederleinii. Apoptosis assay, cell cycle assay, aerobic glycolysis inhibition assays, and analysis of oncogenic protein expression were conducted to investigate the anticancer effect of the most selective fraction. This study demonstrated that the ethyl acetate (EA) fraction exhibited the strongest cytotoxicity and selectivity against the T47D cells (IC₅₀= 19.31 µg/mL; Selectivity Index (SI) = 18.94). EA fraction significantly induced apoptosis, impeded the cell cycle, and diminished glucose consumption and lactate secretion, mostly starting at the concentration 2xIC₅₀in 48 h. The EA fraction also significantly downregulated the expression of p-mTOR, c-Myc, and Hexokinase 2 (HK2) proteins in modulating apoptosis, cell cycle, and aerobic glycolysis. However, HIF-1α inhibition might also contribute to the anticancer activity of the EA fraction. In conclusion, the ethyl acetate fraction of S. doederleinii exerted considerable anticancer effects against T47D cells. The fraction can be further developed to cure luminal A patients through more intensive studies.