Combinatorial effects of curcumin, morin, and phyllanthin in MDA-MB-231 and MCF-7 breast cancer cell lines

Abstract: OBJECTIVES: To evaluate the cytotoxic efficacy and interaction dynamics of curcumin, morin, and phyllanthin – individually and in dual (C + M) and triple (C + M + P) combinations – in estrogen receptor-positive (MCF-7) and triple-negative (MDA-MB-231) breast cancer cell lines. MATERIALS AND METHODS: Cytotoxicity was assessed by MTT assay after 24 h of treatment with varying concentrations of the phytochemicals. Half-maximal inhibitory concentrations were determined, and interaction effects were analyzed using the Combination Index (CI) model. Two-way ANOVA was used to quantify compound contributions and the statistical significance of interactions. RESULTS: The Curcumin + Morin (C + M) combination exhibited additive cytotoxic effects in both MDA-MB-231 (CI = 0.881) and MCF-7 (CI = 0.860) cells, showing significant dose-dependent inhibition ( P < 0.001). Addition of phyllanthin (C + M + P) further enhanced cytotoxicity, resulting in additive interaction in MDA-MB-231 (CI = 0.864) and synergistic interaction in MCF-7 (CI = 0.684). Contribution analysis indicated that phyllanthin, despite low individual potency, accounted for approximately 50%–55% of total cytotoxicity by amplifying the effects of curcumin and morin. CONCLUSIONS: Combinations of curcumin, morin, and phyllanthin demonstrate subtype-dependent cytotoxic enhancement, with synergy evident in hormone receptor-positive breast cancer cells. These findings support the potential of phytochemical co-treatment as a complementary approach to improve therapeutic efficacy through multi-pathway modulation while minimizing toxicity.