Mastoparan induces apoptosis in B1 6F10-Nex2 melanoma cells via the intrinsic mitochondrial pathway and displays antitumor activity in vivo

作者：de Azevedo Ricardo A^*; Figueiredo Carlos R; Ferreira Adilson K; Matsuo Alisson L; Massaoka Mariana H; Girola Natalia; Auada Aline V V; Farias Camyla F; Pasqualoto Kerly F M; Rodrigues Cecilia P; Barbuto Jose A; Levy Debora; Bydlowski Sergio P; de Sa Junior Paulo L; Travassos Luiz R; Lebrun Ivo

来源：Peptides, 2015, 68: 113-119.

DOI：10.1016/j.peptides.2014.09.024

• Mastoparan
• Apoptosis
• Intrinsic pathway
• Melanoma
• Antitumor effects in vivo

Mastoparan is an a-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 (Delta psi(m)), 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.

• 出版日期2015-6