Synthetic phosphoethanolamine induces apoptosis through caspase-3 path by decreasing expression of bax/bad protein and changes cell cycle in melanoma

• Grant number: 12/51513-5
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: January 01, 2013
• End date: June 30, 2013
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Durvanei Augusto Maria
• Grantee: Durvanei Augusto Maria
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

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 cytotoxicity was evaluated by MTT assay and PHO-S was cytotoxic in melanoma cells but not in fibroblasts with IC 50% 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 G2IM, besides increasing number of apoptotic cells, inducing caspase-3 activity and decreasing Bad/Bax protein expression. 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. (AU)