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Exploring the cytotoxicity of phytochemicals: Comparative analysis of single and combination therapies in multiple cell lines

Haghani F, Ashaari S, Ganjooei NA, Behnam B, Kesharwani P, Sahebkar A

Toxicon : official journal of the International Society on Toxinology, 2025

Abstract

We aimed to determine and compare the cytotoxic effects of curcumin (Cur), gingerol (Gin), berberine (Ber), resveratrol (Res), baicalin (Bai), and epigallocatechin-3-gallate (EGCG) both individually and in combination, across MCF-7, 3T3, A549, PC-12, and HT-29 cell lines. The findings also showed that IC50 values were not achieved for Bai and EGCG in all exposed cell lines. Furthermore, Cur was the most potent cytotoxic agent in monotherapy. In combination therapy, the Cur + Res combination indicated the most inhibitory effect in MCF-7 cells. The most inhibitory effects were for Res + Bai and Cur + Res combinations in 3T3 cells. In the resistant A549 cells, the combined administration of phytochemical enhanced cytotoxic effects. The combinations of Cur + Gin, Cur + Res, and Cur + Ber were identified as the most effective inhibitors in the PC-12 cell line. In HT-29 cells, the combinations of Cur + Gin, Cur + Res, Cur + Ber, and Cur + Res + Gin exhibited the highest inhibitory effects. Based on these findings, Cur was the most cytotoxic agent in monotherapy, while Cur + Res exhibited the greatest cytotoxicity in combination therapy. Moreover, combination therapy led to increased cytotoxic actions of phytochemicals in resistant cells. Therefore, combinational administration is recommended for future anti-cancer studies, as it allows for the use of lower concentrations of each phytochemical.

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