Investigating the Cytotoxic and Apoptotic Effects of Telmisartan, both independently and in combination with Doxorubicin, on a Lung Cancer Cell Line

Telmisartan (Tel), an angiotensin receptor blocker, has shown potential in enhancing the anticancer efficacy of Doxorubicin (Dox) against lung cancer, a leading cause of global mortality. This study investigated the cytotoxic and apoptotic effects of Tel alone and in combination with Dox on A549 lung cancer cells. Cells were divided into four groups (control, Tel-treated, Dox-treated, and Tel + Dox-treated) and exposed to six drug concentrations. After 72 hours, cytotoxicity and IC50 values were assessed, followed by BCL-2 expression analysis and apoptosis quantification. Results showed that Tel alone had modest cytotoxicity, but its combination with Dox significantly enhanced anticancer activity, achieving 86.78% cytotoxicity at 800 µg/ml. The combination therapy reduced Dox’s IC50 from 292.46 µg/ml to 72.21 µg/ml (CI = 0.45), indicating strong synergy. The dose reduction index revealed a significant decrease in the required Dox dosage when combined with Tel. Furthermore, Tel treatment significantly reduced BCL-2 expression (P < 0.0458) compared to the control, similar to the reduction observed in Dox-treated cells. Apoptosis analysis demonstrated a higher percentage of apoptotic cells in Tel-treated groups compared to controls, with Dox inducing slightly greater apoptosis than Tel, though not statistically significant. These findings suggest that Telmisartan enhances Doxorubicin's anticancer effects by inducing apoptosis through a BCL-2-dependent mechanism, highlighting its potential as a combinational therapeutic strategy for lung cancer treatment.