Studying synergistic anticancer effects of repurposed AT1B losartan with antidiabetics metformin, rosiglitazone in triple-negative breast cancer cells.

This article investigates the effects of losartan, metformin, and rosiglitazone on triple-negative breast cancer (TNBC) with an intent to repurpose these drugs for cancer therapy. The cytotoxicity of the compounds was evaluated through the MTT assay, where cells were exposed to each drug, both singularly and in combinations, over 48 h. The median inhibitory concentration (IC50) for each drug was calculated using nonlinear regression via GraphPad Prism, yielding IC50 values of 1231 μM for losartan, 30.37 μM for metformin, and 267.1 μM for rosiglitazone. The study highlights a synergistic effect particularly between losartan and metformin in TNBC, revealing a 1.6-fold increase in potency at a fixed 1:1 combination ratio. This combination facilitated enhanced cell growth inhibition over individual drug treatments, particularly at concentrations below 1280 μM. Furthermore, when losartan was combined with rosiglitazone, there was a notable augmentation in synergistic effects, underscoring improved efficacy, as seen by right-shifted dose-response curves and increased maximal responses at concentrations of 320 μM or higher. In assays with MDA-MB-231 cells, strong synergy was detected at minimal doses when losartan and metformin were combined, leading to significant dose reduction indices (DRIs) of 21.92 for losartan and 17.247 for metformin. In contrast, findings indicated that while losartan moderately inhibited growth within 48 h, the combination treatment did not yield any additional synergism with rosiglitazone at lower doses. The study concludes that although losartan and rosiglitazone exhibit strong synergy in inhibiting TNBC growth, the concurrent administration of these drugs at lower dosages presents limitations in achieving further synergistic or additive effects.