Comparison of ABQ-48 Multimodal Cytotoxicity Mechanism Against Lung, Colorectal, and Breast Cancer Cells

Cancer continues to be a significant cause of death worldwide, particularly cancers with high incidence and mortality such as colorectal, breast, and lung, motivating the continued search for novel anticancer agents. Among potential new molecules with anticancer effects, members of the benzazolo[3,2-<i>a</i>]quinolinium salts (BQs) family, including ABQ-48, have shown promising cytotoxic activity in various cancer models. This study aimed to evaluate the cytotoxic potential and mechanism of action of ABQ-48 (3-amino-7-benzylbenzimidazo[3,2-<i>a</i>]quinolinium chloride) across non-small cell lung carcinoma (NCI-H460), colorectal adenocarcinoma (COLO-205), and breast ductal carcinoma (T-47D) cell lines. Cancer cells were treated for 48 h with ABQ-48, cisplatin, or vehicle, and cytotoxicity was assessed by determining IC₅₀ by fluorescence analysis. Mechanistic evaluation included Annexin V apoptosis detection, caspase-3/7/8 activation assays, mitochondrial membrane permeability analysis, and DNA fragmentation assessment. ABQ-48 exhibited dose-dependent cytotoxicity in all three cancer cell lines, with IC₅₀ values of 6.02 µM (NCI-H460), 14.33 µM (COLO-205), and 33.59 µM (T-47D), surpassing cisplatin's overall efficacy. Annexin V assays confirmed apoptotic induction, while caspase activation demonstrated engagement of both intrinsic and extrinsic pathways. ABQ-48 demonstrates potent anticancer activity through activation of multiple programmed cell death mechanisms, supporting further investigation as promising therapeutic candidate.