title: Mastoparan induces apoptosis in B16F10-Nex2 melanoma cells via the intrinsic mitochondrial pathway and displays antitumor activity in vivo.
abstract: Mastoparan is an α-helical and amphipathic tetradecapeptide obtained from the venom of the wasp Vespula lewisii. This peptide exhibits a wide variety of biological effects, including antimicrobial activity, increased histamine release from mast cells, induction of a potent mitochondrial permeability transition and tumor cell cytotoxicity. Here, the effects of mastoparan in malignant melanoma were studied using the murine model of B16F10-Nex2 cells. In vitro, mastoparan caused melanoma cell death by the mitochondrial apoptosis pathway, as evidenced by the Annexin V-FITC/PI assay, loss of mitochondrial membrane potential (ΔΨm), generation of reactive oxygen species, DNA degradation and cell death signaling. Most importantly, mastoparan reduced the growth of subcutaneous melanoma in syngeneic mice and increased their survival. The present results show that mastoparan induced caspase-dependent apoptosis in melanoma cells through the intrinsic mitochondrial pathway protecting the mice against tumor development.
authors.affiliation: Biochemistry and Biophysics Laboratory, Butantan Institute, SP, Brazil. Electronic address: ricardoaazevedo@hotmail.com.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: de Azevedo
authors.affiliation: Experimental Oncology Unit (UNONEX), Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, SP, Brazil.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Figueiredo
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, SP, Brazil.
authors.forename: Adilson K
authors.initials: AK
authors.lastname: Ferreira
authors.affiliation: Experimental Oncology Unit (UNONEX), Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, SP, Brazil.
authors.forename: Alisson L
authors.initials: AL
authors.lastname: Matsuo
authors.affiliation: Experimental Oncology Unit (UNONEX), Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, SP, Brazil.
authors.forename: Mariana H
authors.initials: MH
authors.lastname: Massaoka
authors.affiliation: Experimental Oncology Unit (UNONEX), Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, SP, Brazil.
authors.forename: Natalia
authors.initials: N
authors.lastname: Girola
authors.affiliation: Biochemistry and Biophysics Laboratory, Butantan Institute, SP, Brazil.
authors.forename: Aline V V
authors.initials: AV
authors.lastname: Auada
authors.affiliation: Experimental Oncology Unit (UNONEX), Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, SP, Brazil.
authors.forename: Camyla F
authors.initials: CF
authors.lastname: Farias
authors.affiliation: Biochemistry and Biophysics Laboratory, Butantan Institute, SP, Brazil.
authors.forename: Kerly F M
authors.initials: KF
authors.lastname: Pasqualoto
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, SP, Brazil.
authors.forename: Cecília P
authors.initials: CP
authors.lastname: Rodrigues
authors.affiliation: Cell and Molecular Therapy Center NUCEL-NETCEM, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: José A
authors.initials: JA
authors.lastname: Barbuto
authors.affiliation: Laboratory of Genetics and Molecular Hematology (LIM31), University of São Paulo School of Medicine, SP, Brazil.
authors.forename: Debora
authors.initials: D
authors.lastname: Levy
authors.affiliation: Laboratory of Genetics and Molecular Hematology (LIM31), University of São Paulo School of Medicine, SP, Brazil.
authors.forename: Sérgio P
authors.initials: SP
authors.lastname: Bydlowski
authors.affiliation: Laboratory of Genetics, Butantan Institute, SP, Brazil.
authors.forename: Paulo L
authors.initials: PL
authors.lastname: de Sá-Junior
authors.affiliation: Experimental Oncology Unit (UNONEX), Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, SP, Brazil.
authors.forename: Luiz R
authors.initials: LR
authors.lastname: Travassos
authors.affiliation: Biochemistry and Biophysics Laboratory, Butantan Institute, SP, Brazil.
authors.forename: Ivo
authors.initials: I
authors.lastname: Lebrun
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects; D009368:Neoplasm Transplantation; D018384:Oxidative Stress; D010455:Peptides / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D014862:Wasp Venoms / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D014862:Wasp Venoms; C037500:mastoparan
keywords: Antitumor effects in vivo; Apoptosis; Intrinsic pathway; Mastoparan; Melanoma