Anti-cancer effects of Plumbago zeylanica L. against human triple-negative breast cancer: Insights from network pharmacology and in-vitro experimental validation

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks targeted therapeutic options due to the absence of estrogen, progesterone and HER2 receptors. The present study explores the anti-cancer potential of Plumbago zeylanica L. (P. zeylanica), a medicinal plant known for its diverse pharmacological properties. Using a combined approach of network pharmacology and in-vitro experimental validation, present study investigates the bioactive compounds in P. zeylanica and their interactions with molecular targets involved in TNBC progression. Network pharmacology identified 380 potential targets of P. zeylanica and 2890 TNBC-associated targets, intersecting to reveal 129 common targets. Gene enrichment and pathway analyses highlighted key pathways, including EGFR resistance, HIF-1 signaling and breast cancer pathways. Molecular docking and molecular dynamics (MD) simulations further supported these findings, revealing strong binding affinities between P. zeylanica compounds, particularly zeylanone and critical proteins like PARP1, ESR1 and HSP90AA1. In-vitro assays on MDA-MB-231 cells showed a dose- and time-dependent reduction in cell viability, with an IC₅₀ of 90.79 μg/mL. Apoptosis induction was confirmed through Annexin V/PI staining, with 23 % early apoptosis and 0.90 % late apoptosis. Furthermore, cell cycle analysis revealed G1 phase arrest, inhibiting cell proliferation. These results suggest that P. zeylanica is a promising natural therapeutic agent against TNBC, warranting further research for potential clinical applications in cancer treatment.