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Registration Number

0221U101224, 0119U101606 , R & D reports

Title

The role of metabolic reprogramming of tumor cells in the development of cancer stem cells (CSCs) phenotype: contribution of adaptor protein Ruk/CIN85

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Head

Drobot Liudmyla B., Доктор біологічних наук

Registration Date

18-01-2021

Organization

Department for special training National academy of science of Ukraine at Kiev University

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  It was revealed the participation of the Ruk / CIN85 adapter protein in the metabolic reprogramming of LLC cells associated with the suppression of their aggressiveness. A decrease in lactate dehydrogenase A activity in LLC cells with down-regulation of the adapter protein (subline B1) and lactate content in the medium of their cultivation was demonstrated. It was found that in cell extracts there was a decrease in the activities of copper and quinone-containing amino oxidases (lysyl oxidase, semicarbazide-sensitive amino oxidase, diamine oxidase), as well as aldehyde dehydrogenase, in the case of inhibition of the adapter protein expression. At the same time the total intracellular concentration of aldehydes did not change. In addition, a decrease in the level of hydrogen peroxide was found, with a corresponding significant inhibition of the activities of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase. In vivo simulations of Lewis lung carcinoma (LLC) in mice showed that the application of semicarbazide, an irreversible inhibitor of copper and quinone-containing amino oxidases, normalized both morphometric and biochemical parameters in the tissue of the targeted organ lung. During the reporting period, a comparative analysis of the expression of pro-inflammatory and anti-inflammatory cytokines in tumor lines of small cell lung cancer, sensitive and resistant to cisplatin NCI-H69/CPR and NCI-H69 was performed. TLR4 expression in cisplatin-resistant lung cancer cell culture was found to be twice as high as in the original, and the expression of the proinflammatory mediator IFN-γ was 28-fold higher, while the expression of TGF-β and TNF-α were 25-fold and 16-fold lower, respectively After the addition of teichoic acid, which acts as a ligand for TLR4, the expression of TLR4 and all studied cytokines was inhibited by 4.2, 1.4, 1.6 and 1.2 times, respectively. The data obtained might indicate that teichoic acid of bacterial origin pr

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Garmanchuk Liudmyla V
Horak Iryna R
Dovbinchuk Taiisa V
Drobot Liudmyla B
Latishko Nelli V.
Senchylo Natalya V.
Skaterna Tetyana D.
Zeisler Yuliia V
Shelest Dmitro V.

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2021-01-18