An attitude on apoptosis resistance as the most important causes of cancer cell growth
An attitude on apoptosis resistance as the most important causes of cancer cell growth
Mohana Kamari,1,*
1. Msc of Molecular Genetic Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.
Introduction: Morphological hallmarks of apoptosis in the nucleus are chromatin condensation and nuclear fragmentation, which are accompanied by rounding up of the cell, reduction in cellular volume (pyknosis), and retraction of pseudopods. Chromatin condensation starts at the periphery of the nuclear membrane, forming a crescent or ring-like structure. The chromatin further condenses until it breaks up inside a cell with an intact membrane, a feature described as karyorrhexis. The plasma membrane is intact throughout the total process. At the later stage of apoptosis, some of the morphological features include membrane blebbing, ultrastructural modification of cytoplasmic organelles, and a loss of membrane integrity. The aim of this study was an attitude toward apoptosis resistance as the most important cause of cancer cell growth.
Methods: This study was investigating an attitude toward apoptosis resistance as the most important cause of cancer cell growth from scientific databases such as Science Direct, Springer, Google Scholar, and PubMed
Results: Apoptosis mechanisms must be understood in order to comprehend the etiology of diseases brought on by disrupted apoptosis. This could thus aid in the creation of medications that specifically target particular apoptotic genes or pathways. Due to their dual roles as initiators and executors of apoptosis, caspases play a crucial role in the process. Three different mechanisms can activate caspases. The intrinsic (or mitochondrial) and extrinsic (or death receptor) routes of apoptosis are the two often discussed starting processes. Both routes ultimately lead to the execution stage of apoptosis, which is a shared pathway. The intrinsic endoplasmic reticulum pathway is a third, less well-known starting pathway. Cancer can be considered as the outcome of a series of genetic alterations in which a normal cell undergoes a malignant transformation. One of the crucial alterations in a cell that results in this malignant transformation is the evasion of cell death. Apoptosis was associated with the removal of possibly cancerous cells, hyperplasia, and tumor development as early as the 1970s, according to Kerr et al. Therefore, decreased apoptosis or its resistance is key to the development of cancer. A malignant cell can develop a decrease in apoptosis or apoptosis resistance in a variety of ways. 1) disrupted the balance of pro-apoptotic and anti-apoptotic proteins, 2) reduced caspase function and 3) impaired death receptor signaling summaries the mechanisms that contribute to evasion of apoptosis and carcinogenesis. A set of physically and functionally related proteins known as the inhibitor of apoptosis proteins control signal transduction, cytokinesis, and apoptosis. They are distinguished by the presence of the protein domain known as the baculovirus IAP repeat (BIR). There are currently eight known IAPs: Livin/ML-IAP (BIRC7), NAIP (BIRC1), c-IAP1 (BIRC2), c-IAP2 (BIRC3), X-linked IAP (XIAP, BIRC4), Survivin (BIRC5), Apollon (BRUCE, BIRC6), and IAP-like protein 2 (BIRC1) (BIRC8). IAPs are naturally occurring caspase inhibitors that work by attaching their conserved BIR domains to the active sites of caspases, increasing the destruction of active caspases, or preventing caspases from interacting with their substrates.
the importance of abnormalities in apoptotic pathways in the development of carcinogenesis, as well as the viability and potential of numerous new apoptosis-targeting therapeutic approaches. Some perplexing and unsettling questions, however, such as whether these therapeutic approaches lead to tumor resistance and whether they may result in the mass death of normal cells, remain unaddressed. If there are any lessons to be learned from the conventional anticancer medications, which kill both normal and tumor cells, have severe side effects, and increase tumor resistance, then this is a real issue. On the other hand, if these compounds that target apoptosis are selectively working on a single pathway or protein, that would be advantageous clinically. Although many inhibitors of the Bcl family of proteins and some pan-IAP inhibitors are among the molecules that enter clinical trials, the majority of them act on multiple targets. Therefore, ongoing research should concentrate on methods that can specifically trigger apoptosis in cancer cells while sparing healthy cells.
Conclusion: The importance of abnormalities in apoptotic pathways in the development of carcinogenesis, as well as the viability and potential of numerous new apoptosis-targeting therapeutic approaches. Some perplexing and unsettling questions, however, such as whether these therapeutic approaches lead to tumor resistance and whether they may result in the mass death of normal cells, remain unaddressed. If there are any lessons to be learned from the conventional anticancer medications, which kill both normal and tumor cells, have severe side effects, and increase tumor resistance, then this is a real issue. On the other hand, if these compounds that target apoptosis are selectively working on a single pathway or protein, that would be advantageous clinically. Although many inhibitors of the Bcl family of proteins and some pan-IAP inhibitors are among the molecules that enter clinical trials, the majority of them act on multiple targets. Therefore, ongoing research should concentrate on methods that can specifically trigger apoptosis in cancer cells while sparing healthy cells.