Penetration of the peptide lactaptin into human cancer cells

Аннотация

Lactaptin, a human milk protein with a molecular weight of 8.6 kDa, is a fragment of human ?casein, which has cytotoxic activity toward mammalian cancer cells in vitro. RL2 is a recombinant analogue of lactaptin, which induces the apoptosis of human cancer cells in culture and suppresses the tumor growth in vivo. It has been shown earlier that RL2 penetrates into both human cancer and nonmalignized cells and binds to cytoskeletal structures. In this process, it induces the apoptosis of cancer cells and does not diminish the viability of normal cells. The mechanism of the penetration of RL2 into human cancer cells has been studied by flow cytometry and fluorescence microscopy using the inhibitors of different endocytosis pathways. It has been shown that RL2 penetrates into cells partly through lipid raft-mediated dynamin-independent pinocytosis and partly through direct penetration across the plasma cell membrane. An analysis of the primary structure of RL2 and the mechanism of its penetration into the cell suggests that it can be assigned to the class of cell-penetrating peptides.