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THE EFFECT OF CHITOSAN ON THE SYNTHESIS OF L-S-NITROSOCYSTEINE THAT PARTICIPATES IN THE REGULATION OF THE M2 PYRUVATE KINASE ISOENZYME ACTIVITY ASSOCIATED WITH EHRLICH ASCITES CELLS PROLIFERATION IN VITRO

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Ignacak J., Zagajewski J., Pałka I., Wiśniewska-Wrona M., Niekraszewicz A.

Progress on Chemistry and Application of Chitin and its Derivatives

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2010

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vol. 15

149 - 158

EN

L-S-nitrosocysteine formation in EAT tumor cells and normal CRL-1636 cells incubated with microcrystalline chitosan was confirmed by RP-HPLC. The metabolite was identified based on UV-VIS spectra. The formation of L-S-nitrosocysteine in EAT tumor cells contributes to decreasing the level of L-cysteine in these cells. L-cysteine as an effector of the bifunctional M2 isoenzyme of pyruvate kinase (PK) initiates its histone kinase activity, which is responsible for histone H1 phosphorylation. A decrease of L-cysteine level in EAT tumor cells contributes to lack of histone H1 phosphorylation by the M2 PK isoenzyme and by the same token to inhibition of EAT cell proliferation.

2

ROLE OF CHITOSAN OLIGOMERS IN REGULATION OF EHRLICH ASCITES TUMOR CELLS PROLIFERATION IN VITRO

100%

Ignacak J., Wiśniewska-Wrona M., Pałka I., Zagajewski J., Niekraszewicz A.

Progress on Chemistry and Application of Chitin and its Derivatives

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2011

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vol. 16

89 - 98

EN

Preliminary studies of proliferation of Ehrlich ascites tumor (EAT) cells and normal mammary gland epithelial cells have demonstrated the process to be inhibited by degradation products of microcrystalline chitosan, i.e. oligomers. Inhibition of proliferation has been also accompanied by a decreased activity of the M2 pyruvate kinase (PK) isoenzyme in nucleoplasm, what may indicate the role of this enzyme in regulation of tumor cell proliferation. Determinations of nitrogen oxide in tumor and normal cells point to a higher level of this endogenous effector in normal cells. An increase of nitrogen oxide levels in Ehrlich ascites tumor cells effected by chitosan oligomers may indicate increased nitrosylation, and particularly an increased amount of compounds containing sulfhydryl groups and their participation in regulation of nucleoplasm M2 PK isoenzyme activity. Chitosan oligomers have smaller molecules as compared to microcrystalline chitosan and for this reason appear to be more effective than the latter in acting upon the negatively charged cell membrane surfaces, thus contributing to proliferation inhibition.

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EFFECT OF OLIGOCHITOSANS ON EXPRESSION OF INOS GENE IN EHRLICH ASCITES TUMOUR IN VITRO

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Ignacak J., Wiśniewska-Wrona M., Dulińska-Litewka J., Pałka I., Zagajewski J., Niekraszewicz A.

Progress on Chemistry and Application of Chitin and its Derivatives

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2012

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vol. 17

141 - 148

EN

Oligochitosans obtained through degradation of macromolecules of chitosan with a high degree of deacetylation turned out to be biologically active, contributing to an increase of nitric oxide levels in Ehrlich ascites tumor (EAT) cells through inducing expression of the isoform of inducible nitric oxide synthase (iNOS) gene. An increase of NO levels in EAT cells in the presence of the investigated oligochitosans might contribute to nitrosylation of L-cysteine – an allosteric effector of the M2 isoenzyme of pyruvate kinase (PK), which switches the PK kinase activity, responsible for ATP synthesis, to the histone kinase activity that may participate in histone H1 phosphorylation. Lack of the histone activity of the PK M2 isoenzyme may contribute to decreased histone H1 phosphorylation and thus inhibit EAT cells proliferation.

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3 Progress on Chemistry and Application of Chitin and its Derivatives

1 2012

1 2011

1 2010

3 Ignacak J.

3 Niekraszewicz A.

3 Pałka I.

3 Wiśniewska-Wrona M.

3 Zagajewski J.

1 Dulińska-Litewka J.

THE EFFECT OF CHITOSAN ON THE SYNTHESIS OF L-S-NITROSOCYSTEINE THAT PARTICIPATES IN THE REGULATION OF THE M2 PYRUVATE KINASE ISOENZYME ACTIVITY ASSOCIATED WITH EHRLICH ASCITES CELLS PROLIFERATION IN VITRO

ROLE OF CHITOSAN OLIGOMERS IN REGULATION OF EHRLICH ASCITES TUMOR CELLS PROLIFERATION IN VITRO

EFFECT OF OLIGOCHITOSANS ON EXPRESSION OF INOS GENE IN EHRLICH ASCITES TUMOUR IN VITRO