Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Department of Pharmacology, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo, Brazil.
Biomed Pharmacother. 2018 Jul;103:18-28. doi: 10.1016/j.biopha.2018.03.135. Epub 2018 Apr 24.
Phosphoethanolamine (PEA) is a fundamental precursor during the biosynthesis of cell membranes phospholipids. In the past few years, it has been described as a potential antitumor agent. In previous studies, we demonstrated that PEA showed antitumor properties in vitro and in vivo in a wide range of tumor cell lines. Herein, we showed that PEA possesses cytotoxic properties and notably revealed to induce caspase-independent cell death. Of interest, we provided evidence that PEA inhibits melanoma cells proliferation through the reduction of C-RAF. Molecular docking of PEA evidenced that this compound indeed fits satisfactory in the binding site located between the dimers of C-RAF protein with 107,01 Å and score of -29,62. Also, PEA arrested A2058 cells at G2/M phase in the cell cycle. Moreover, cell proliferation, migration and adhesion capacities of A2058 cells were also inhibited by PEA. Most importantly, PEA inhibited tumor growth of melanoma tumors and prolonged survival rate of mice. Also, PEA induced a significant immune response in a syngeneic metastatic melanoma model. Taken together, these data indicate that PEA is a promising candidate for future developments in cancer field.
磷酸乙醇胺（PEA）是细胞膜磷脂生物合成过程中的基本前体。在过去的几年中，它已被描述为一种有潜力的抗肿瘤药物。在之前的研究中，我们证明了 PEA 在广泛的肿瘤细胞系中具有体内和体外的抗肿瘤特性。在此，我们证明 PEA 具有细胞毒性，并显著显示诱导 caspase 非依赖性细胞死亡。有趣的是，我们提供的证据表明，PEA 通过减少 C-RAF 来抑制黑素瘤细胞的增殖。PEA 的分子对接表明，该化合物确实与 C-RAF 蛋白二聚体之间的结合位点吻合良好，结合距离为 107.01 埃，得分为-29.62。此外，PEA 使 A2058 细胞在细胞周期中停滞在 G2/M 期。此外，PEA 还抑制了 A2058 细胞的增殖、迁移和黏附能力。最重要的是，PEA 抑制了黑色素瘤肿瘤的生长，并延长了荷瘤小鼠的存活率。此外，PEA 在同种转移性黑色素瘤模型中诱导了显著的免疫反应。综上所述，这些数据表明 PEA 是癌症领域未来发展的有前途的候选药物。
