Abstract
Autophagy is a process of self-degradation that plays an important role in removing damaged proteins, organelles or cellular fragments from the cell. Under stressful conditions such as hypoxia, nutrient deficiency or chemotherapy, this process can also become the strategy for cell survival. Autophagy can be nonselective or selective in removing specific organelles, ribosomes, and protein aggregates, although the complete mechanisms that regulate aspects of selective autophagy are not fully understood. This review summarizes the most recent research into understanding the different types and mechanisms of autophagy. The relationship between apoptosis and autophagy on the level of molecular regulation of the expression of selected proteins such as p53, Bcl-2/Beclin 1, p62, Atg proteins, and caspases was discussed. Intensive studies have revealed a whole range of novel compounds with an anticancer activity that inhibit or activate regulatory pathways involved in autophagy. We focused on the presentation of compounds strongly affecting the autophagy process, with particular emphasis on those that are undergoing clinical and preclinical cancer research. Moreover, the target points, adverse effects and therapeutic schemes of autophagy inhibitors and activators are presented.
Highlights
Autophagy, directly translated as ‘self-eating’, is an evolutionary conservative process, found in all eukaryotic cells—from single-cell yeasts to much more complex multicellular mammalian organisms [1]
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A paper recently published by Lopiccolo and co-authors describes in vitro and in vivo studies using chloroquine and nelfinavir as a combination therapy in non-small cell lung cancer (NSCLC) treatment
Summary
Directly translated as ‘self-eating’, is an evolutionary conservative process, found in all eukaryotic cells—from single-cell yeasts to much more complex multicellular mammalian organisms [1]. The introduction of the term ‘autophagy’ was proposed in February 1963 during the conference titled ‘Ciba Foundation Symposium on Lysosomes’ which took place in London [2] This process participates in intracellular degradation of damaged or redundant proteins with a long half-life as well as other unnecessary cytoplasm components [3,4]. Autophagy provides an organism’s homeostasis and prevent it from redundant components accumulation inside the cell [5] This process is involved in surfactant formation or red blood cells ripening [3]. ADCD occurs in all eukaryotic cells performing important functions, for example, it is an adaptation mechanism to stressful conditions, as it provides cells with a constant supply of nutrients essential for sustaining key life processes. The target points, adverse effects and therapeutic schemes of autophagy inhibitors and activators are presented in tables
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