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

Abstract

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.