がんの科学と治療

Synthetic Phosphoethanolamine Induces Apoptosis Through Caspase-3 Pathway by Decreasing Expression of Bax/Bad Protein and Changes Cell Cycle in Melanoma

Abstract

Adilson Kleber Ferreira, Renato Meneguelo, Salvador Claro Neto, Gilberto Orivaldo Chierice and Durvanei Augusto Maria

Phospholipids are potential antineoplastic agents that are abundant constituents of the cell membrane of eukaryotes and are supposed to be involved in specific intracellular signaling such as cell death. The aim of this study was to assess the in vitro and in vivo antitumor effects of synthetic phosphoethalomanine (PHO-S) on B16F10 murine melanoma cells and normal human fibroblasts. The cytotoxicty was evaluated by MTT assay and PHO-S was cytotoxic in melanoma cells but not in fibroblasts with IC50% of 1.4 mg/ml to melanoma cells. In vivo antitumor activity was evaluated in a mice model subcutaneously injected with B16F10 melanoma cells. The mice treated with PHO-S in all concentrations showed a decrease of the tumor growth and metastasis. Cytometry analysis showed that the PHO-S blocked DNA synthesis, decreased number of melanoma cells in S phase and G2/M, besides increasing number of apoptotic cells, inducing caspase-3 activity and decreasing Bad/Bax protein expression. Histologically, the dorsal tumors in the control group showed pigmented nodular masses with high vascularization and pleomorphic tumor cells. In the treated group, PHO-S reduction vascularization intratumoral with increased of collagen fibers and infiltrates neutrophils. The data indicate that PHO-S is a lipid compound potential with proapoptotic and antiproliferative effects but further work will be necessary to elucidate the antitumor mechanisms.