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THE ROLE OF CHITOSAN IN AKT KINASE REGULATION ACTIVITY

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Ignacak J., Wiśniewska-Wrona M., Dulińska-Litewka J., Pałka I., Kucharska M., Kazimierski J.

Progress on Chemistry and Application of Chitin and its Derivatives

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2016

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vol. 21

73-82

EN

A decrease in migration of tumor cells incubated with the investigated chitosan preparations was correlated with a decreased activity of MMP-2 and MMP-9 metalloproteinases, what significantly affected inhibition of tumor cell proliferation. In the investigations of the effects of various chitosan preparations on expression of PCNA, Akt and β-catenin in the normal human 184A1 cells and in breast carcinoma MCF7 cells evaluated at the protein level, significant differences in inhibition of expression of selected genes were noted in the tumor cells. Similarly as in the case of human cells, in mouse cells, the differences in expression of the investigated genes involved solely the Ehrlich carcinoma cells. In the presence of the investigated chitosan preparations, there was observed inhibition of expression of the N-cadherin, β-catenin, Akt and PCNA genes. In case of p21 protein, its level increased, similarly as in the human breast carcinoma cells, what may also be related to phosphorylation of the protein, its capture by the cytosol and prolonging its half-life as compared to the non-phosphorylated form. In case of the normal human 181A1 cells and mouse CRL 1636 cells, no significant alterations were noted in expression of the investigated genes in presence of the employed chitosan preparations.

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THE ROLE OF OLIGOCHITOSANS IN AKT KINASE REGULATION

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Ignacak J., Wiśniewska-Wrona M., Dulińska-Litewka J., Pałka I., Kucharska M.

Progress on Chemistry and Application of Chitin and its Derivatives

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2015

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vol. 20

73-81

EN

Among characteristic properties of cancers, there is their increased glycolytic activity.Contrary to normal cells, neoplastic cells use anaerobic glycolysis, even when a sufficient amount of oxygen is available. The intensity of the process is associated with a considerable demand for energy in the form of ATP. Akt, which - acting through the mTOR pathway - activates the HIF-1 factor, which in turn activates hexokinase that participates in glucose phosphorylation, stimulates the transport of glucose to cells via increasing glucose transporters (GLUT) and activates lactate dehydrogenase (which transforms pyruvate to lactate). Chitosan, as well as products of its degradation - oligochitosans - contribute to inhibiting the activity of the Akt kinase, and thus contribute to inhibiting excessive glycolytic activity of Ehrlich ascites tumor (EAT) cells and to decreasing proliferation of these cells.

3

INHIBITION OF EHRLICH ASCITES TUMOUR (EAT) CELLS PROLIFERATION THROUGH CHITOSAN-MEDIATED REGULATION OF ACTIVITY OF THE AKT PATHWAY

100%

Ignacak J., Wiśniewska-Wrona M., Dulińska-Litewka J., Pałka I., Kucharska M.

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EN

Isoenzyme M2 pyruvate kinase, which is a marker of cancer transformation, can take both tetramer (cytosol) and dimer (nucleus) forms. The former is responsible for ATP synthesis, and the latter demonstrates histone H1 kinase activity. Regulation of the expression of pyruvate kinase through which Akt controls the expression of genes involved in Ehrlich ascites tumour (EAT) cell proliferation, migration and death, also involves cross-talk with the other signalling pathways, transcription factors and co-regulatory proteins such as β-catenin and c-Myc. Treatment of EAT cells with chitosans significantly reduced their proliferation (by 45-60%), expression of nuclear β-catenin, c-Myc as well as cell migration. After 48–72 hours of treatment of the cell with oligochitosans, lower levels of p-Akt were detected. Simultaneously, decreased expression of isoenzyme M2 PK protein levels was observed. The dimeric form (nucleus) can participate in H1 histone phosphorylation, which contributes to increased EAT cell proliferation.

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3 Progress on Chemistry and Application of Chitin and its Derivatives

1 2016

1 2015

1 2014

3 Dulińska-Litewka J.

3 Ignacak J.

3 Kucharska M.

3 Pałka I.

3 Wiśniewska-Wrona M.

1 Kazimierski J.

THE ROLE OF CHITOSAN IN AKT KINASE REGULATION ACTIVITY

THE ROLE OF OLIGOCHITOSANS IN AKT KINASE REGULATION

INHIBITION OF EHRLICH ASCITES TUMOUR (EAT) CELLS PROLIFERATION THROUGH CHITOSAN-MEDIATED REGULATION OF ACTIVITY OF THE AKT PATHWAY