Select bioavailable metabolites from Lippia citriodora and Olea europaea extracts exhibit anticancer effects on pancreatic cancer cell lines

Abstract

Phenolic compounds are widely recognized for their anti-proliferative and chemopreventive properties, making them potential candidates for cancer therapy. Lippia citriodora (LC) and Olea europaea (OE) are two phenolic-rich plant extracts with established antitumor activity. Despite their distinct phytochemical compositions, a clinical intervention study identified nine common bioavailable metabolites in human plasma following ingestion of these extracts. This study aimed to evaluate the anticancer effects of selected shared bioavailable metabolites identified in human plasma after ingestion of LC and OE extracts, oleuropein (Oleu), vanillic acid sulfate (VA-Sul), and homovanillic acid sulfate (HVA-Sul), and compared them to the parent compounds, on pancreatic cancer cells in vitro. Using two human pancreatic cancer cell lines, the metabolites were assessed for their effects on cell viability, apoptosis, and cell cycle progression. Among the shared metabolites, Oleu exhibited the highest plasma bioavailability and significantly inhibited cancer cell growth by reducing the cell cycle progression. VA-Sul and HVA-Sul also suppressed tumor cell proliferation, likely through non-apoptotic mechanisms. In conclusion, these findings underscore the therapeutic relevance of bioavailable phenolic metabolites and highlight the importance of evaluating metabolite-specific bioactivity in the development of plant-based interventions for pancreatic cancer.