Abstract B41: Antitumoral and angiostatic activities in skin secretion of frog <i>Phyllomedusa bicolor</i>
Authors: Hanneke van Zoggel, Yamina Hamma-Kourbali, Cécile Galanth, Ali Ladram, Pierre Nicolas, José Courty, Mohamed Amiche, Jean Delbé
Journal: Clinical Cancer Research (2010)

Abstract The skin secretions of neotropical and South American frogs contains large amounts of a wide range of biological active peptides. Commonly studied are small peptides with antimicrobial activities as the Dermaseptin family. These peptides constitute a primitive immune defence mechanism and are able to disrupted the membranes of microbes and, subsequently, to inhibit their growth leading to cell death. Some of these antimicrobial peptides also present an antitumoral activity whereby they use a similar disrupting mechanism on the plasma membrane of the tumoral cells [1]. Therefore, intense research is now performed on the secretions from amphibian skin to discover new pharmacological agents, especially useful for drug-based cancer treatments. In this study we have postulated that the skin secretions from the South American frog Phyllomedusa bicolor contain such molecules and we reported antitumoral and angiostatic activities from a crude extract of these secretions [2]. After a two steps chromatography procedure, we have identified one of the bioactive compounds in this crude extract as Dermaseptin B2 (Drs B2) [3]. Drs B2 is a well known antimicrobial peptide which is 33-amino acid residues long. This natural α-helical peptide consist of a cationic NH2-terminal part (residues 1 to 23) predicted to form an amphipathic α-helix that is followed by a hydrophobic tail (residues 24 to 33). A synthetic Drs B2 peptide was prepared and tested for its antitumoral and angiostatic activities. Results obtained with this synthetic molecule were equal to those obtained by testing the crude extract in vitro. Thus, Drs B2 inhibited the growth of different human tumoral cell lines like the prostatic adenocarcinoma cell line PC3 and the mammary carcinoma cell line MDA-MB231 when cultured on plastic or in soft agar with an EC50 of 1–2 μM. Drs B2 was also able to inhibit non adherent human tumoral cells like the Raji and LB-EBV lymphoma cell lines with the same efficiency. It is noteworthy that Drs B2 showed an inhibitory effect on non tumoral cells like NIH-3T3 and primary mouse embryonic cells but only when concentrations higher than 10 μM where used. Furthermore, Drs B2 was evaluated for its effect on endothelial cells growth and was able to inhibit to growth of the adult bovine aortic endothelial cells (ABAE) in vitro. Moreover, Drs B2 could also block the capillary network formation induced by FGF-2 of these cells when cultured on collagen in a Montesano model. In conclusion, Drs B2 could represent a new interesting pharmacological leader molecule against the proliferation of human tumoral cells that now need to be evaluated on different cancer cell types in vitro but also in vivo in animal models. Besides that, also the mechanism of action of Drs B2 on tumoral cells has to be clear before further pharmacological development. Citation Information: Clin Cancer Res 2010;16(7 Suppl):B41