DNA damage, apoptosis and cell cycle disruption: Antitumor effects of a novel tin(IV) complexes

Introduction: Platinum-based chemotherapeutics like cisplatin are widely used against cancer but are limited by toxicity and drug resistance. Organotin(IV) complexes offer a promising alternative with enhanced efficacy and distinct mechanisms. Here, we evaluated the anticancer activity of dibutyl and diphenyl organotin(IV) complexes and investigated their mechanisms of action across multiple cancer cell lines. Material and Method: Synthesis of Organotin(IV) Complexes: Dibutyl and diphenyl organotin(IV) (Bu-Sn and Ph-Sn) complexes were synthesized following established protocols. The purity and structural confirmation of the complexes were verified using spectroscopic techniques. Anti-cancer activities: The following human cell lines were used in this study: T-47D (breast carcinoma), HCT116 (colorectal carcinoma), AsPC-1 (pancreatic adenocarcinoma), and MCF-10A (non-tumorigenic mammary epithelial). Following manufactures protocol MTT assay is utilized for the determination of half maximum inhibitory concentration (IC 50 ). The mode of cell death (apoptosis and necrosis) investigated in cell lines via flow cytometry using the Annexin V and propidium iodide (PI) staining method. Analysis of cell cycle with flow cytometry performed to determine the changes in the cell cycle for each cell lines utilizing cisplatin as a reference drug. Subcellular distribution of the organotin(IV) complexes was evaluated by ICP-MS. Treated cells were fractionated into major cellular compartments to determine the predominant localization of the complexes. DNA damage induced by the organotin(IV) complexes was assessed using the Comet assay, allowing quantification of treatment-related DNA strand breaks. Results and Discussion: Bu-Sn exhibited strong cytotoxic activity across all tested cancer cell lines (IC₅₀ < 3.00 µM), with particularly high potency against T-47D human breast cancer cells (IC₅₀ = 0.53 µM). Importantly, it showed minimal toxicity toward non-cancerous MCF-10 cells, demonstrating a favorable level of selectivity. In contrast, Ph-Sn displayed only limited cytotoxic activity. Mechanistically, Bu-Sn induced G1 phase arrest and triggered dose-dependent apoptosis in T-47D cells. Subcellular analysis revealed predominant nuclear accumulation (32% for Bu-Sn, 24% for Ph-Sn), correlating with pronounced DNA damage observed in Comet assays, suggesting that nuclear targeting and genotoxic stress underlie its anticancer activity. Conclusion: Two organotin(IV) complexes containing dibutyl and diphenyl groups were synthesized and fully characterized. The dibutyl complex exhibited strong cytotoxic activity across multiple cancer cell lines while sparing non-malignant cells. Mechanistic studies indicated that these tin complexes primarily target DNA, inducing cell cycle arrest and apoptosis, ultimately leading to cancer cell death.