Functional reprogramming of melittin by Pluronic® F-127 enables anticancer selectivity with attenuated hemolytic activity

Introduction Conventional anticancer treatments have a number of limitations, including significant toxicity to healthy cells. Therefore, it is necessary to explore new therapeutic methods and strategies that utilize bioactive compounds with high selectivity for cancer cells while simultaneously limiting toxicity. Melittin is a membrane-active antimicrobial peptide known for its significant anticancer potential; nevertheless, its pronounced hemolytic activity greatly restricts its therapeutic use. In this work, strategy to functionally separate anticancer efficacy from hemolytic toxicity using Pluronic ® F-127 (PF127) is investigated. Methods A549 human lung adenocarcinoma and HeLa cervical carcinoma cell lines were subjected to treatment with melittin (0.5–50 µg/mL), PF127 (1–5%), and their combinations. Cancer cell viability was assessed using the MTT assay, and cell apoptosis was evaluated using flow cytometry. Cell migration capabilities of treated cancer cells were determined using scratch assay. The hemolytic activity of melittin and the melittin/Pluronic ® F-127 combination, an indicator of toxicity to cell membranes, was assessed using hemolysis of human red blood cells (RBCs). Results Our studies confirmed that melittin displays anticancer effects against A549 and HeLa cell lines in a dose-dependent manner and this effect is further augmented in the presence of PF127. Migration experiments revealed significant suppression of cancer cell motility after exposure to melittin/PF127. Furthermore, the use of the melittin/PF127 combination reduced the hemolytic activity of melittin in relation to RBCs. Conclusions Co-treatment of cancer cells with melittin and PF127 enables selective anticancer effects while attenuating hemolytic activity. The findings indicate that the toxicity of membrane-active peptides and their anticancer effectiveness can be separated through formulation employment, underscoring PF127 as a promising element in the strategic development of safer melittin-based anticancer approaches.