Exploring the Therapeutic Potential of Oxo berberine Compound in Arcangelisia flava Root Extract for Breast Cancer Treatment: Metabolite Profiling, Pharmacological Network Analysis, and In Silico and In Vitro Evaluation.

OBJECTIVE

Chemotherapy treatments for breast cancer often entail side effects and drug resistance. Arcangelisia flava root extract (AFRE) shows potential as an anti-cancer agent, but understanding its compounds and mechanisms against breast cancer remains limited. This study aims to identify potential compounds in AFRE and shed light on its actions against breast cancer.

METHODS

Compounds in AFRE were identified via LC-MS/MS. ADMET software evaluated absorption and bioavailability. Molecular anti-cancer mechanisms were predicted using network pharmacology with tools like Cytoscape, GeneCards, Disgenet, STRING, GO, KEGG pathways, and SRplot. Interaction between oxo berberine and key breast cancer receptors was analyzed through molecular docking with PyRx Autodock Vina and Biovia Discovery Studio. Cytotoxicity was assessed using the MTT method on T47D cells, and flow cytometry evaluated the potential to inhibit the cell cycle and induce apoptosis.

RESULT

A total of 16 active compounds were identified through LC-MS/MS, with oxo berberine being the most abundant at 41.43%. Importantly, it exhibited anti-cancer properties by interacting with 84 genes and affecting 13 signaling pathways related to breast cancer. We found that oxo berberine had a stronger negative binding affinity with PI3KCA, TP53, BCL2, CDK1, EGFR, and MAPK14 than the native ligand, which was supported by molecular docking results. In vitro validation supported these results even more, showing that AFRE treatment caused more T47D cells to die (36.6%) than the control and doxorubicin, as well as more cells to gather in the G1 phase.

CONCLUSION

In summary, this evidence highlights the potent anti-cancer effects of oxo berberine in AFRE against breast cancer.