A lactoferricin B/buforin chimeric peptide causes a rapid, selective, prolonged cytotoxic effect and induces apoptosis in hpv18-positive cervical cancer cells

Abstract

This study focuses on the chimeric peptide KKWQWK-Ahx-RLLRRLLR and its interactionwith cancer cells, specificallyHPV18-positive cervical cancerHeLa andCa Ski cells. Themainobjective of this studywas tounderstand themode of actionof thischimerarelatedtoitscytotoxicactivity, aswell as the internalization processes and the type of cell death induced. For this purpose, several invitro and in vivo assays were performed, showing that the up take of the chimera is not energy-dependent and could involve a passive transport process. The results suggested that chimera internalization can be mediated by a specific interaction of the peptide with molecules on the cell membrane. The cytotoxic effect of the chimera in cervical cancer cells causes severe morphological changes, including rounding, shrinking, and vacuole formation. It was also determined that the chimera primarily induces early and late apoptosis in He Lacells, without causing necrosis,and activates caspases 3and7. The chimera was localized in both the cytoplasm and the nucleus of the cancer cells, suggesting that the peptide could interact with intracellular targets. Inconclusion, this study provides abroader understanding of the mechanism of action of the KKWQWK-Ahx-RLLRRLLR chimera on cancer cells,highlighting its ability to induce a fast, selective, and significant lycytotoxic effect in cervical cancer cells,which involves cell death through the apoptotic pathway. The toxicity assaysin Galleria mellonella and zebra fish showed that the chimera is safe and can be considered for preclinical studies.This study demonstrated that the chemical binding of two sequences with low activity produces a chimeric entity with enhanced cytotoxic activity capable of cellular internalization and inducement of apoptosis.