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

## TL;DR

ABQ-48, a new compound, shows strong cancer-fighting effects against lung, colorectal, and breast cancer cells by triggering cell death mechanisms.

## Contribution

ABQ-48 is a novel alkaloid with potent cytotoxicity and a multi-pathway mechanism of action against multiple cancer types.

## Key findings

- ABQ-48 induces apoptosis through intrinsic and extrinsic pathways in lung, colorectal, and breast cancer cells.
- ABQ-48 shows superior cytotoxicity compared to cisplatin in tested cancer cell lines.
- The compound causes mitochondrial damage and DNA fragmentation across all three cancer types.

## Abstract

Among main causes of death, cancer continues to be a significant cause worldwide. The diversity of cancer types and etiology creates the need for novel and active anticancer treatments. Our study evaluated the cytotoxic potential and mechanism of action of ABQ-48 (3-amino-7-benzylbenzimidazo[3,2-a]quinolinium chloride), a novel unnatural alkaloid of the BQ family, across three human cancer cell lines including: non-small cell lung carcinoma (NCI-H460), colorectal adenocarcinoma (COLO-205), and breast ductal carcinoma (T-47D). Our findings demonstrate that ABQ-48 has anticancer activity at low micromolar levels, especially on lung cancer cells, through the activation of multiple programmed cell death, mitochondrial damage and DNA fragmentation with consistent mechanistic profile across the three cancer types. Notably, ABQ-48 demonstrated superior cytotoxicity compared to cisplatin, a well-established and currently FDA approved and applied chemotherapy agent, supporting the potential and further investigation of ABQ-48 as a promising therapeutic candidate.

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-a]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-a]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.