Role of mTOR Pathway in Modulation of Radiation Induced Bystander Effects

Author(s):  
Neha Verma ◽  
Ashu Bhan Tiku
Author(s):  
Svetlana V. Kostyuk ◽  
Aleksei V. Ermakov ◽  
Anna Yu. Alekseeva ◽  
Tatiana D. Smirnova ◽  
Kristina V. Glebova ◽  
...  

Biology ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 191 ◽  
Author(s):  
Eman Elbakrawy ◽  
Savneet Kaur Bains ◽  
Scott Bright ◽  
Raheem AL-Abedi ◽  
Ammar Mayah ◽  
...  

Ionizing Radiation (IR), especially at high doses, induces cellular senescence in exposed cultures. IR also induces “bystander effects” through signals released from irradiated cells, and these effects include many of the same outcomes observed following direct exposure. Here, we investigate if radiation can cause senescence through a bystander mechanism. Control cultures were exposed directly to 0, 0.1, 2, and 10 Gy. Unirradiated cells were treated with medium from irradiated cultures or with exosomes extracted from irradiated medium. The level of senescence was determined post-treatment (24 h, 15 days, 30 days, and 45 days) by β-galactosidase staining. Media from cultures exposed to all four doses, and exosomes from these cultures, induced significant senescence in recipient cultures. Senescence levels were initially low at the earliest timepoint, and peaked at 15 days, and then decreased with further passaging. These results demonstrate that senescence is inducible through a bystander mechanism. As with other bystander effects, bystander senescence was induced by a low radiation dose. However, unlike other bystander effects, cultures recovered from bystander senescence after repeated passaging. Bystander senescence may be a potentially significant effect of exposure to IR, and may have both beneficial and harmful effects in the context of radiotherapy.


2019 ◽  
Vol 20 (12) ◽  
pp. 1217-1226 ◽  
Author(s):  
Arunaksharan Narayanankutty

Background: Phosphoinositide 3-kinase (PI3Ks) is a member of intracellular lipid kinases and involved in the regulation of cellular proliferation, differentiation and survival. Overexpression of the PI3K/Akt/mTOR signalling has been reported in various forms of cancers, especially in colorectal cancers (CRC). Due to their significant roles in the initiation and progression events of colorectal cancer, they are recognized as a striking therapeutic target. Objective: The present review is aimed to provide a detailed outline on the role of PI3K/Akt/mTOR pathway in the initiation and progression events of colorectal cancers as well as its function in drug resistance. Further, the role of PI3K/Akt/mTOR inhibitors alone and in combination with other chemotherapeutic drugs, in alleviating colorectal cancer is also discussed. The review contains preclinical and clinical evidence as well as patent literature of the pathway inhibitors which are natural and synthetic in origin. Methods: The data were obtained from PubMed/Medline databases, Scopus and Google patent literature. Results: PI3K/Akt/mTOR signalling is an important event in colorectal carcinogenesis. In addition, it plays significant roles in acquiring drug resistance as well as metastatic initiation events of CRCs. Several small molecules of natural and synthetic origin have been found to be potent inhibitors of CRCs by effectively downregulating the pathway. Data from various clinical studies also support these pathway inhibitors and several among them are patented. Conclusion: Inhibitors of the PI3K/mTOR pathway have been successful for the treatment of primary and metastatic colorectal cancers, rendering the pathway as a promising clinical cancer therapeutic target.


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