They induce autophagy as part of their mechanism of action. This physicochemical property and the resultant changes are basis for their anticancer, antiprotozoal, antibacterial, and antiviral activities. Alkylphosphocholines (APCs) are phospholipid-derived agents that cause changes in cell signaling by enriching in cell membranes including the lipid rafts. Autophagy either can have a protective function for cell survival or promote cell death. It has essential roles in keeping the cellular homeostasis and functions in cellular differentiation, control of cellular growth, cell defense, and promotes tissue remodeling and acclimatization. Therefore, autophagy-dependent cellular responses need to be well understood in order to improve the chemotherapeutic outcome.Īutophagy is derived from a Greek word (αυτοϕαγϵἷν) meaning ‘self-eating’ and is a bulk degradation process, which includes the lysosomal-dependent degradation and recycling of components of eukaryotic cells. APCs display differential autophagy induction capabilities in different cancer cell types. Autophagy is a double-edged sword and may result in chemotherapeutic resistance as well as cancer cell death when apoptotic pathways are inactive. However, treatment with APC derivatives will lead to dephosphorylation (hence deactivation) of mTOR and thus induces autophagy. mTOR is a down-stream target for Akt, the activation of which suppresses autophagy. In a high fraction of human cancers, constitutively active oncoprotein Akt1 suppresses autophagy in vitro and in vivo. APCs include miltefosine, perifosine, and erufosine, which represent the first-, second- and third generation of this class, respectively. They interfere with phospholipid turnover and thus modify signaling chains, which start from the cell membrane and modulate PI3K/Akt/mTOR, Ras-Raf-MAPK/ERK and SAPK/JNK pathways. They induce autophagy through inhibition of the Akt/mTOR cascade. protein kinase B), which mediates cell survival and cause cell cycle arrest. Alkylphosphocholine (APC) derivatives represent a novel class of antineoplastic agents that inhibit the serine–threonine kinase Akt ( i.e. One of the major regulators of this process is mTOR, which inhibits the downstream pathway of autophagy following the activation of its complex 1 (mTORC1). chaperone mediated autophagy, microautophagy, macroautophagy, and selective autophagy. Based on the nature of these materials, their size and degradation rate, four types of autophagy have been described, i.e. Autophagy is a highly conserved multistep process and functions as passage for degrading and recycling protein aggregates and defective organelles in eukaryotic cells.
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