Polyphenolic Diversity, Antioxidant Activity, and Anticancer Potential of Celtis australis L. Fruits: New Insights

Celtis australis L. was selected for investigation due to its traditional medicinal use and the limited number of studies available, particularly concerning its anticancer potential. This study examined the phenolic composition, the antioxidant activity, and the anticancer effects of methanolic, ethanolic, and aqueous extracts of C. australis L. The in vitro cytotoxic efficacy was assessed with the MTT assay on six tumor cell lines (HeLa, MV4-11, OCI-AML3, DAOY, OSN-76, and U-138-MG) and two non-cancerous cell lines (HEK293T and hCMEC/D3). C. australis L. extracts exhibited moderate antioxidant activity, as evidenced by their high IC₅₀ values (110-436 μg/mL). The FRAP reducing power was low (2.09-6.24 mg AAE/g), and the aqueous extract was least active, with IC₅₀ values ranging from 152 to 207 μg/mL in the ABTS assay. The HPLC-ESI-MS/MS analysis indicated that the extracts contain a variety of phenolic compounds dominated by neochlorogenic acid, chlorogenic acid, procyanidin B2, (-)-epicatechin, isoquercitrin, rutin, phloretin, and delphindin-3,5-diglucoside. Cytotoxicity assays demonstrated a dose-dependent reduction in cell viability, with DAOY cells exhibiting the highest sensitivity. Water extract exhibited significant inhibitory effects at elevated concentrations, whereas ethanol extract showed greater potency at intermediate doses (7.5%-50%) for specific cancer cell lines. Methanol extract exhibited a more gradual impact and showed reduced potency at elevated doses. According to IC₅₀ values, the ethanolic extract was the most efficacious in four out of the six cancer cell lines, whereas water extract demonstrated notable potency for OCI-AML3 and OSN-76 but were less effective on normal cells, suggesting selectivity based on cell type. The selectivity index indicated that methanol exhibited the highest selectivity, especially against OSN-76, MV4-11, OCI-AML3, and HeLa cell lines, implying its predilection for cancer cells over normal cells. Ethanol demonstrated notable selectivity, particularly toward OSN-76 and MV4-11. Conversely, water extracts exhibited minimal selectivity across all strains. In summary, methanol and ethanol extracts demonstrate the best potential for selective anticancer efficacy.