Anti-melanoma activity of hybrid peptide P18 and its mechanism of action.
The anticancer properties and mechanism of action of a hybrid peptide -P18 were investigated. It had significant cytotoxic activity against human melanoma cells and low toxicity to normal NIH-3T3 cells. It also induced cell death via necrosis rather than classical apoptosis. The peptide targets the cells membrane, causing a sustained depolarization of transmembrane potential resulting in the cells swelling and bursting, thereby triggering cytolysis. P18 peptide initially binds to the melanoma cell membrane via electrostatic interaction, causing the cell membrane to rupture. The effect may be mediated by the amphiphilic alpha-helical structure of P18 peptide, coupled with changes in ion channels and an increase in plasma membrane permeability that eventually leads to melanoma cell death.
Huang
Wenli
W
Institute for Nanobiomedical Technology and Membrane Biology, West China Hospital, Sichuan University, 610041 Chengdu, Sichuan, China.
Lu
Li
L
Shao
Ximing
X
Tang
Chengkang
C
Zhao
Xiaojun
X
D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells
D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; C447608:P18 antimicrobial peptide