Comparison of Catechol-Induced Expression Levels of ATM, ATR, BAX, BCL2, and CCND1 Genes Between Parental and Epirubicin-Resistant NSCLC Cells

<strong>Objective:</strong> This study investigated the apoptotic effects of catechol on lung cancer by comparing gene expression levels in parental lung cancer cells (P-H1299), Epirubicin-HCl resistant lung cancer cells (R H1299), and healthy fibroblast cells (Bj). <strong>Materials and Methods:</strong> The cytotoxic effects of catechol on cells were determined using a Cell Titer-Blue Cell viability assay. To understand the apoptotic effect of catechol, caspase-3/7 activity was measured using a kit. RT-PCR was used to measure the mRNA expression of the ATM, ATR, BAX, BCL2, CCND1, and PCNA genes. <strong>Results:</strong> The IC₅₀ values for catechol were determined to be 58 µM for P-H1299, 90 µM for R-H1299, and 207 µM for BJ cells, indicating selective cytotoxicity towards cancerous cells. Caspase 3 activity and Bax/Bcl-2 ratio analyses revealed increased apoptosis in cancer cells, especially in drug-resistant R-H1299 cells. Gene expression analysis revealed increased ATM and ATR mRNA levels in P-H1299 cells, indicating the most DNA damage. Molecular docking studies have suggested that catechol's lower DNA binding affinity compared with known intercalating agents, such as Epirubicin and Doxorubicin, implies a mechanism of action reliant on reactive oxygen species rather than direct DNA intercalation. Efficient antioxidant mechanisms facilitate high survival rates of healthy cells. <strong>Conclusion: </strong>Results indicate that catechol cytotoxicity is mainly caused by ROS-induced DNA damage, offering a novel strategy for targeting both parental and drug-resistant lung cancer cells. This study proposes a promising direction for the development of safer and more effective chemotherapy drugs that spare healthy cells and potential clinical applications for catechol.