In vitro and in vivo analyses of the biological activity of RGD peptides towards Ab Bomirski melanoma.
The RGD sequence is present in many extracellular matrix proteins and intracellular proteins, including caspases. Synthetic RGD peptides may affect adhesion, migration and tumour metastasis, or directly induce apoptosis. Several RGD peptides were synthesised, and their anti-adhesive and cytotoxic properties were analysed in vitro. The most active peptide (poly RGD) was also tested in vivo to assess its modulatory activity on melanoma growth. Synthetic RGD peptides inhibit the adhesion of Ab melanoma cells to fibronectin. Poly RGD significantly inhibits primary tumour growth. There was no observed cytotoxicity of poly RGD towards Ab cells in a medium with 10% serum; however, under the same conditions, the anti-adhesive effect of poly RGD was still visible. Experiments on Jurkat cells indicated a weak cytotoxicity of poly RGD and a significant cytotoxicity of GRGDNP (the reference cytotoxic peptide), retained only under serum-free conditions. The anti-tumour effect of poly RGD observed in the Ab Bomirski melanoma model is probably due to an anti-adhesive mechanism. The proapoptotic activity of RGD peptides is dependent on the absence of serum.
Okrój
Marcin
M
Department of Cell Biology, Intercollegiate Faculty of Biotechnology Medical University of Gdańsk, Debinki 1, 80-211 Gdańsk, Poland.
Dobrzańska-Paprocka
Zuzanna
Z
Rolka
Krzysztof
K
Bigda
Jacek
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D006224:Cricetinae; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008545:Melanoma / Q000188:drug therapy*; D009842:Oligopeptides / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
D005353:Fibronectins; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid