Novel Anti-proliferative Application of Telmisartan and Candesartan: Synergistic Repurposing Strategy Against Colorectal Cancer

Background: Colorectal cancer (CRC) remains a significant global health burden with high mortality and rising resistance to chemotherapy. Angiotensin receptor blockers (ARBs), traditionally used to treat hypertension, have recently been shown to have anti-cancer effects by inhibiting the angiotensin II type 1 receptor (AT1). Objectives: To assess the anti-proliferative effects of telmisartan and candesartan on CRC cells and their synergy with chemotherapy. Materials and Methods: This in vitro study used CRC cell lines to assess viability (MTT assay), growth (soft agar), migration (wound healing), cell cycle and apoptosis (flow cytometry), and gene expression of B-cell lymphoma 2 (BCL2), vascular endothelial growth factor (VEGF), and AT1 by quantitative polymerase chain reaction. Results: Telmisartan and candesartan inhibited CRC cell growth in a time- and dose-dependent fashion, with IC₅₀ values ranging from 63 to 274 µM. When combined with doxorubicin or 5-fluorouracil, they reduced chemotherapy IC₅₀ values by up to 11.6-fold, indicating synergistic cytotoxicity (CI < 1). Both ARBs suppressed wound closure by more than 60%, decreased colony formation by over 50%, induced G0/G1 cell cycle arrest (42% to 66%), and markedly increased apoptosis (54.4% with candesartan vs. 4.6% in controls). Additionally, gene expression analysis revealed more than a twofold downregulation of BCL2, VEGF, and AT1. Conclusion: Telmisartan and candesartan show anti-cancer effects in CRC and synergise with chemotherapy, supporting their potential for repurposing.