This study aimed to examine if methanolic extracts of Pulsatilla vulgaris Mill. can inhibit HeLa cell proliferation through the modulation of cancer-related signaling pathways. The cytotoxicity and chemical composition of P. vulgaris leaves and root extracts were also determined. Research showed that root extract of P. vulgaris inhibited 12 signaling pathways in a cervical cancer cell line and the most potent activation inhibition was observed for MYC, Notch, Wnt, E2F, Ets, Stat3, Smad, Hdghog, AP-1, and NF-κB, at a concentration of 40 µg/mL. The methanolic extracts of P. vulgaris enhanced apoptotic death and deregulated cellular proliferation, differentiation, and progression toward the neoplastic phenotype by altering key signaling molecules required for cell cycle progression. This is the first study to report the influence of P. vulgaris on cancer signaling pathways. Additionally, our detailed phytochemical analysis of the methanolic extracts of P. vulgaris gives a conclusion that compounds, which strongly suppressed the growth and proliferation of HeLa cancer cells were mainly triterpenoid saponins accompanied by phenolic acids.
Keywords: HeLa cells; luciferase reporter gene vectors; natural products; phenolic acids; saponins.