Anticancer mechanisms of Poikilospermum suaveolens root fraction: ethnopharmacological relevance, signaling pathways, and in vitro/in silico studies on MCF-7 cells.

[ETHNOPHARMACOLOGICAL RELEVANCE] Poikilospermum suaveolens (Blume) Merr., traditionally used in Indonesian folk medicine, has been employed for its reputed anticancer properties. However, scientific evidence elucidating its molecular mechanisms against breast cancer remains limited.

[AIM OF THE STUDY] This study aimed to evaluate the cytotoxic and molecular effects of the ethyl acetate root fraction of P. suaveolens (FEAPs) on MCF-7 breast cancer cells, focusing on apoptosis induction, signaling pathway modulation, and mechanistic insights through in vitro and in silico approaches.

[MATERIALS & METHODS] Roots of P. suaveolens were collected, identified, and extracted. Ethyl acetate fractions were obtained by sequential solvent extraction. Phytochemical profiling was conducted using LC-HRMS/MS. Cytotoxicity was assessed by resazurin assay; antioxidant capacity by DPPH assay. Expression of malignancy, apoptosis, cell cycle, and autophagy-related genes was evaluated via RT-PCR. Morphological changes were observed microscopically. Molecular docking analyzed interactions between major compounds and Caspase-3 and Caspase-7.

[RESULTS] FEAPs exhibited moderate cytotoxicity (IC: 128.46 ± 0.75 ppm) against MCF-7 cells. LC-HRMS/MS revealed flavonoids, phenolics, and triterpenoids as dominant constituents. PCR showed downregulation of AKT, mTOR, and STAT-3, and upregulation of FADD, CASP-8, and CASP-9. Cyclin D1 and CDK-1 expression decreased, indicating cell cycle inhibition. Molecular docking revealed swertiajaponin exhibited strong affinity to Caspase-7.

[CONCLUSION] FEAPs exerts anticancer effects in MCF-7 breast cancer cells by modulating multiple signalling pathways and likely promoting caspase mediated apoptosis, supporting its traditional use as an anticancer remedy.