title: Cytotoxic Activity and Antiproliferative Effects of Crude Skin Secretion from Physalaemus nattereri (Anura: Leptodactylidae) on in vitro Melanoma Cells.
abstract: Anuran secretions are rich sources of bioactive molecules, including antimicrobial and antitumoral compounds. The aims of this study were to investigate the therapeutic potential of Physalaemus nattereri skin secretion against skin cancer cells, and to assess its cytotoxic action mechanisms on the murine melanoma cell line B16F10. Our results demonstrated that the crude secretion reduced the viability of B16F10 cells, causing changes in cell morphology (e.g., round shape and structure shrinkage), reduction in mitochondrial membrane potential, increase in phosphatidylserine exposure, and cell cycle arrest in S-phase. Together, these changes suggest that tumor cells die by apoptosis. This skin secretion was also subjected to chromatographic fractioning using RP-HPLC, and eluted fractions were assayed for antiproliferative and antibacterial activities. Three active fractions showed molecular mass components in a range compatible with peptides. Although the specific mechanisms causing the reduced cell viability and cytotoxicity after the treatment with crude secretion are still unknown, it may be considered that molecules, such as the peptides found in the secretion, are effective against B16F10 tumor cells. Considering the growing need for new anticancer drugs, data presented in this study strongly reinforce the validity of P. nattereri crude secretion as a rich source of new anticancer molecules.
authors.affiliation: Laboratory of Toxinology, Department of Physiological Sciences/IB, University of Brasília, Brasília/DF, CEP 70.910-900, Brazil. andreabiologa@gmail.com.|Laboratory of Biochemistry and Protein Chemistry, Department of Cell Biology/IB, University of Brasília, Brasília/DF, CEP 70.910-900, Brazil. andreabiologa@gmail.com.
authors.forename: Andréa
authors.initials: A
authors.lastname: Cruz e Carvalho
authors.affiliation: Laboratory of Toxinology, Department of Physiological Sciences/IB, University of Brasília, Brasília/DF, CEP 70.910-900, Brazil. caprias@gmail.com.|Laboratory of Biochemistry and Protein Chemistry, Department of Cell Biology/IB, University of Brasília, Brasília/DF, CEP 70.910-900, Brazil. caprias@gmail.com.
authors.forename: César Augusto Prías
authors.initials: CA
authors.lastname: Márquez
authors.affiliation: Department of Genetics and Morphology/IB, University of Brasília, Brasília/DF, CEP 70.910-900, Brazil. razevedo@unb.br.
authors.forename: Ricardo Bentes
authors.initials: RB
authors.lastname: Azevedo
authors.affiliation: Department of Genetics and Morphology/IB, University of Brasília, Brasília/DF, CEP 70.910-900, Brazil. bygra1@gmail.com.|Faculty of Ceilândia, University of Brasília, Ceilândia/DF, CEP 72.220-140, Brazil. bygra1@gmail.com.
authors.forename: Graziella Anselmo
authors.initials: GA
authors.lastname: Joanitti
authors.affiliation: Laboratory of Toxinology, Department of Physiological Sciences/IB, University of Brasília, Brasília/DF, CEP 70.910-900, Brazil. osmindo@unb.br.
authors.forename: Osmindo Rodrigues
authors.initials: OR
authors.lastname: Pires Júnior
authors.affiliation: Laboratory of Biochemistry and Protein Chemistry, Department of Cell Biology/IB, University of Brasília, Brasília/DF, CEP 70.910-900, Brazil. wagnerf@unb.br.
authors.forename: Wagner
authors.initials: W
authors.lastname: Fontes
authors.affiliation: Laboratory of Toxinology, Department of Physiological Sciences/IB, University of Brasília, Brasília/DF, CEP 70.910-900, Brazil. mscastro@unb.br.|Laboratory of Biochemistry and Protein Chemistry, Department of Cell Biology/IB, University of Brasília, Brasília/DF, CEP 70.910-900, Brazil. mscastro@unb.br.
authors.forename: Mariana S
authors.initials: MS
authors.lastname: Castro
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001001:Anura / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008546:Melanoma, Experimental / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D012867:Skin / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents
keywords: Physalaemus nattereri; antitumoral activity; anurans; cytotoxicity; melanoma; skin secretion