Molecular Insights into the Interaction Between Metformin and Caffeine: Time-Dependent Antagonism and Modulation of p53 Signaling in Cancer Cells
Abstract
Background: : Cancer remains a major global health challenge, with treatment efficacy li-mited by drug resistance and adverse effects. Drug repurposing offers opportunities for novel anticancer strategies. This study evaluated the cytotoxic, antiproliferative, and pro-apoptotic effects of metformin and caffeine, alone and in combination, in human cancer cell lines, and their potentialinteraction mechanisms.
Methods:: Human cervical carcinoma (HeLa), lung adenocarcinoma (A549), and colorectal carcinoma (HT29) cell lines were treated with metformin (0.05–50 mM) and caffeine (0.5–5 mM), alone or combined, for 24 and 48 h. Cell viability and proliferation were assessed using Trypan Blue and sulforhodamine B (SRB) assays. Apoptosis was analyzed by Annexin V/propidium iodide flow cytometry, and p53 expression in HeLa cells was determined by ELISA. Statistical analysis was performed using one-way ANOVA with Tukey’s post hoc test.
Results:: Metformin induced dose- and time-dependent cytotoxicity in all tested cell lines, with the lowest IC₅₀ values observed in HeLa and A549 cells after 48 h (2.28 and 3.30 mM, respectively; p < 0.05). Caffeine showed moderate antiproliferative activity, with the strongest effects at 2.03 mM in HeLa and 2.01 mM in HT29 cells (p < 0.05). The combined treatment produced effects that varied depending on both the cell line and exposure time. At earlier time points, transient synergistic effects were observed in certain cell lines, particularly HeLa;…
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Evidence Hub reads this as a preprint, done in cell cultures (in vitro), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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