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

ABSTRACT

Phospholipids are potential antineoplastic agents that are abundant constituents of the cell membrane ofeukaryotes 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 pleomorphictumor cells. In the treated group, PHO-S reduction vascularization intratumoral with increased of collagen fibersand infiltrates neutrophils. The data indicate that PHO-S is a lipid compound potential with proapoptotic andantiproliferative effects but further work will be necessary to elucidate the antitumor mechanisms.