Anti-proliferative and cytotoxic activity of pentadactylin isolated from Leptodactylus labyrinthicus on melanoma cells.
Nowadays, the emergence of resistance to the current available chemotherapeutic drugs by cancer cells makes the development of new agents imperative. The skin secretion of amphibians is a natural rich source of antimicrobial peptides (AMP), and researchers have shown that some of these wide spectrum molecules are also toxic to cancer cells. The aim of this study was to verify a putative anticancer activity of the AMP pentadactylin isolated for the first time from the skin secretion of the frog Leptodactylus labyrinthicus and also to study its cytotoxic mechanism to the murine melanoma cell line B16F10. The results have shown that pentadactylin reduces the cell viability of B16F10 cells in a dose-dependent manner. It was also cytotoxic to normal human fibroblast cells; nevertheless, pentadactylin was more potent in the first case. The studies of action mechanism revealed that pentadactylin causes cell morphology alterations (e.g., round shape and shrinkage morphology), membrane disruption, DNA fragmentation, cell cycle arrest at the S phase, and alteration of mitochondrial membrane potential, suggesting that B16F10 cells die by apoptosis. The exact mechanism that causes reduction of cell viability and cytotoxicity after treatment with pentadactylin is still unknown. In conclusion, as cancer cells become resilient to death, it is worthwhile the discovery of new drugs such as pentadactylin that induces apoptosis.
Libério
Michelle S
MS
Department of Cell Biology, Brazilian Center for Protein Research, Institute of Biology, University of Brasilia, Brasilia, DF, CEP 70910-900, Brazil.
Joanitti
Graziella A
GA
Azevedo
Ricardo B
RB
Cilli
Eduardo M
EM
Zanotta
Lanuse C
LC
Nascimento
Anna C
AC
Sousa
Marcelo V
MV
Pires Júnior
Osmindo R
OR
Fontes
Wagner
W
Castro
Mariana S
MS
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001001:Anura / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008545:Melanoma / Q000503:physiopathology*; D051379:Mice; D012867:Skin / Q000737:chemistry / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D003603:Cytotoxins