Investigating the anti-proliferative effects of benzenesulfonamide derivatives on human lung cancer cells; an in-vitro analysis study

Introduction: Lung cancer remains one of the leading causes of cancer-related mortality worldwide, necessitating the exploration of novel therapeutic agents. Benzenesulfonamide derivatives have garnered attention for their potential anti-cancer properties. Objectives: This study aims to investigate the anti-proliferative effects of these compounds on human lung cancer cells and to elucidate the underlying pathways involved in their mechanism of action. Materials and Methods: In this in-vitro study, we investigated the cytotoxic effects of acetazolamide, a pan inhibitor, along with its parent compound C3 and its derivatives C4 and C6 against A549 lung cancer cells. We evaluated key intracellular parameters including pH levels, reactive oxygen species (ROS) production, and the expression of carbonic anhydrases 9 and 12. To assess cell viability and death, we employed the acridine orange/propidium iodide assay, which allowed us to differentiate between live and dead cells. Results: The results of this study indicated that the compounds C3, C4, C6, and acetazolamide effectively reduced the proliferation of A549 lung cancer cells after 72 hours of treatment. Notably, C3 was associated with an increase in ROS levels, suggesting a potential mechanism for its cytotoxicity. In contrast, C6 demonstrated a reduction in ROS levels, while C4 exhibited no significant effect on ROS production. All tested compounds were found to decrease intracellular pH, which may contribute to their anti-proliferative effects. Conclusion: The findings highlight the promising potential of benzenesulfonamide derivatives as effective anti-proliferative agents against A549 lung cancer cells. The diverse mechanisms through which these compounds exert their cytotoxic effects, including modulation of ROS levels and intracellular pH, underscore their multifaceted nature in targeting cancer cell viability.