Ecliptae Herba extracts suppress cell proliferation and induce cell apoptosis of ovarian cancer cells by inactivating PI3K/AKT signaling pathway

Background: Among all the gynaecologic malignancies, ovarian cancer (OV) has the highest mortality rate, and herbal plants have been regarded as an alternative strategy for ovarian cancer therapy. Accumulating evidence indicates that the aboveground part of Eclipta prostrata (L.) L., known as Ecliptae Herba (EH), has anti-cancer activity and can contribute to the management of gynaecological disorders treatment. However, the application and the mechanism of EH against OV remain unexplored. Methods: A cell proliferation assay was first performed to validate the inhibitory effect of EH extracts on ovarian cancer cells. Network pharmacology was then employed to recognize potential bioactive compounds and target genes of EH. A Venn diagram was built to obtain the common targets of EH and OV and the protein-protein interaction (PPI) network of EH-OV correlated target genes was established by STRING. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment approaches were adopted to further reveal the molecular mechanism. Drug-compound-target-pathway-disease network of EH in OV treatment was constructed. The expression of the predicted targets, cell cycle changes and cell apoptosis levels were analyzed to confirm the predicted mechanism of EH. Results: EH extracts suppressed the proliferation of human ovarian cancer cells in a concentration- and time-dependent manner. Ten bioactive compounds and 290 compound-associated targets were collected for EH-OV common targets exploration. A total of 74 EH-OV correlated genes were gathered and enrichment analysis identified phosphatidylinositide 3-kinases (PI3K)/AKT signaling pathway as the main machinery. Drug-compound-target-pathway-disease network indicated the polypharmacological effect of EH. Finally, EH extracts were confirmed to inhibit cell proliferation and induce cell apoptosis of ovarian cancer cells by inactivating PI3K/AKT signaling pathway. Conclusions: This study demonstrated the anti-ovarian cancer activity of whole EH extracts and indicated that EH should be considered as a potential therapeutic strategy for ovarian cancer.

Ecliptae Herba; Ovarian cancer; Network pharmacology; Bioactive compounds; Cell proliferation; Cell apoptosis; PI3K/AKT signaling pathway

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