Evaluation of platinum(II) complexes with 8-Hydroxyquinoline derivative in Electrochemotherapy: Comparative sensitivity of different Cancer cell lines

Platinum-based chemotherapeutics remain a crucial cancer treatment; however, their clinical efficacy is limited by systemic toxicity and acquired drug resistance. The present study evaluates the cytotoxic and mechanistic effects of two platinum(II) complexes of 5,7-dibromo-8-hydroxyquinoline (complex A and complex B) combined with electroporation (electrochemotherapy, ECT) in human colorectal (HT29), breast (MCF7), and ovarian (IGROV-1 and cisplatin-resistant IGROV-1/RDDP) carcinoma cell lines. Both complexes exhibited dose-dependent cytotoxicity that was significantly enhanced by ECT. Complex B showed the highest efficacy in HT29 cells, while MCF7 cells were more responsive to cisplatin-based ECT. Apoptosis was the predominant mode of cell death, supported by Annexin V/7-AAD flow cytometry, with minimal necrosis. Cell cycle analysis indicated treatment-dependent arrest at the G₀/G₁ or G₂/M phase. Importantly, both complexes, particularly complex B, retained strong activity in cisplatin-resistant IGROV-1/RDDP cells. Increased intracellular and DNA-bound platinum levels following ECT confirmed enhanced drug uptake. ECT also significantly inhibited tumor spheroid growth in 3D models. These findings support further preclinical evaluation of these complexes, especially complex B, as promising candidates for ECT-based cancer therapy. • Electroporation markedly enhanced the cytotoxicity and cellular uptake of two platinum(II) complexes across multiple human carcinoma models. • Complex B demonstrated superior apoptotic induction and retained strong activity in cisplatin-resistant human ovarian cancer cells. • Electrochemotherapy effectively inhibited tumor spheroid growth, confirming efficacy in a 3D tumor-mimetic model.