Abstract
Pleural mesothelioma (PM) is an aggressive cancer with limited treatment options, particularly in cisplatin-resistant cases. This study evaluated the anticancer activity of a novel iodine-coordinated compound, dilithium (I) (1→4)-L-D-polyglucopyran triiodide chloride, polypeptide “KC-144,” in cisplatin-sensitive and cisplatin-resistant mesothelioma cell models. Cytotoxic and antiproliferative effects were assessed using MTT assays, colony-forming assays, wound-healing tests, cell cycle analysis, apoptosis detection, mitochondrial membrane potential measurements, and quantification of reactive oxygen and nitrogen species. KC-144 exhibited IC50 values of 0.416 ± 0.046 mg mL-1 in P31 cells, 0.399 ± 0.014 mg mL-1 in cisplatin-resistant P31res1.2 cells, and 0.591 ± 0.021 mg mL-1 in non-malignant MeT-5A cells, indicating moderate selectivity toward malignant cells. Treatment induced oxidative stress, mitochondrial dysfunction, apoptosis, and G0/G1 cell-cycle arrest in mesothelioma cells, accompanied by concentration-dependent inhibition of clonogenic growth. These findings suggest that KC-144 triggers apoptotic pathways at moderate concentrations and direct cytotoxic effects at higher doses. Although the results demonstrate promising antitumor activity, the study is limited by its in vitro design and the narrow therapeutic window observed in normal cells, warranting further mechanistic investigations and in vivo validation before clinical translation.