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

• Authors: Jan Ignacak , Maria Wiśniewska-Wrona , Joanna Dulińska-Litewka , Iwona Pałka , Magdalena Kucharska
• Languages of publication: EN EN

Abstracts

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.

Keywords

EN

Akt kinase - PKB; EAT cells proliferation; M2 pyruvate kinase; chitosan

Discipline

• MEDICAL_BIOLOGY: MEDICAL BIOLOGY

• Publisher: Sieć Badawcza Łukasiewicz - Polskie Towarzystwo Chitynowe
• Journal: Progress on Chemistry and Application of Chitin and its Derivatives
• Year: 2014
• Volume: 19
• Pages: 33-40

Contributors

author

Jan Ignacak

• Chair of Medical Biochemistry, Jagiellonian University, Medical College, Faculty of Medicine

author

Maria Wiśniewska-Wrona

• Institute of Biopolymers and Chemical Fibres

author

Joanna Dulińska-Litewka

• Chair of Medical Biochemistry, Jagiellonian University, Medical College, Faculty of Medicine,

author

Iwona Pałka

• Chair of Medical Biochemistry, Jagiellonian University, Medical College, Faculty of Medicine,

author

Magdalena Kucharska

• Institute of Biopolymers and Chemical Fibres

References

• 1. Hacker E., Wu R., Aloes J.B.: (1960) Carbohydrate metabolism in ascites tumour and HeLa cells: in Amino Acids, Proteins and Cancer Biology (Edsall J.T., ed.) 175-189, Academic Press, New York, London.
• 2. Ganapathy V., Thangaraju M., Prasad M.G.: (2009) Nutrient transporters in cancer: relevance to Warburg hypothesis and beyond. Pharmacol. Ther., 121, 29-40, DOI: 10.1016/j.pharmthera.2008.09.005.
• 3. Young C.D., Anderson S.M.: (2008) Sugar and fat – that’s where it’s at: metabolic changes in tumours. Breast Cancer Res., 10, 202.
• 4. Zhou Q.L., Jiang Z.Y., Holik J., Chawła A., Hagan G.N., Leszyk J., Czech M.P.: (2008) Akt substrate TBCIDI regulates GLUT1 expression through the mTOR pathway in 3T3-LI adipocytes. Biochem. J. 411, 647-655, DOI:10.1042/BJ20071084.
• 5. Robey R.B., Hay N.: (2009) Is Akt the “Warburg kinase”? – Akt-energy metabolism interactions and oncogenesis. Semin. Cancer Biol., 19, 25-31, DOI: 10.1016/j.semcancer.2008.11.010
• 6. Hudson C.C., Liu M., Chiang C.C., Otterness D.M., Loomis D.C., Kaper F., Giaccia A.J., Abraham R.T.: (2002) Regulation of hypoxia-inducible factor 1α expression and function by the mammalian target of rapamycin. Mol. Cell. Biol., 22, 7004-7014, DOI:10.1128/MCB.22.20.7004-7014.2002
• 7. Zhong X.S., Zheng J.Z., Reed E., Jiang B.H.: (2004) SU5416 inhibited VEGF and HIF-1α expression through the PI3K/AKT/p70S6KI signalling pathway. Biochem. Biophys. Res. Commun. 324, 471-480, DOI: 10.1016/j.bbrc.2004.09.082
• 8. Elstrom R.L., Bauer D.E., Buzzai M., Karnauskas R., Harris M.H., Plas D.R., Zhuang H., Cinalli R.M., Alavi A., Rudin C.M., Tompson C.B.: (2004) Akt stimulates aerobic glycolysis in cancer cells. Cancer Res. 64, 3892-3899, DOI:10.1158/0008-5472.CAN-03-2904.
• 9. Lum J.J., Bui T., Gruber M., Gordan J.D., De Berardinis R.J., Covello K.L., Simon M.C., Thompson C.B.: (2007) The transcription factor HIF-1α plays a critical role in the growth factor-dependent regulation of both aerobic and anaerobic glycolysis. Genes Dev. 21, 1037-1049, DOI:10.1101/gad.1529107.
• 10. Brinck U., Eigenbrodt E., Oehmke M., Mazurek S., Fisher G.: (1994) L- and M2-pyruvate kinase expression in renal cell carcinomas and their metastases. Virchovs Arch. 424,177-185, 10.1007/BF00193498.
• 11. Domingo M., Einig C., Eigenbrodt E., Reinacher M.: (1992) Immunohistological demonstration of pyruvate kinase isoenzyme type L in rat with monoclonal antibodies. J. Histochem. Cytochem. 40, 665-673, doi:10.1177/40.5.1374093.
• 12. Steinberg P., Klingelhoffer A., Schafer A., Wust G., Weisse G., Oesch F., Eigenbrodt E.: (1999) Expression of pyruvate kinase M2 in pre-neoplastic hepatic foci of N-nitrosomorpholinetreated rats. Virchows Arch. 434, 213-220, 10.1007/s004280050330.
• 13. Rodriguez-Horche P., Luque J., Perez-Artes E., Pineda M., Pinilla M.: (1987) Comparative kinetic behaviour and regulation by fructose 1,6-P2 and ATP of pyruvate kinase from erythrocytes, reticulocytes and bone marrow cells. Comp. Biochem. Physiol. 87, 553-557.
• 14. Noguchi T., Yamada K., Inoue H., Matsuda T., Tanaka T.: (1987) The L- and R-type isozymes of rat pyruvate kinase are produced from a single gene by use of different promotors. J. Biol. Chem. 262, 14366-14371.
• 15. Yamada K., Noguchi T.: (1999) Regulation of pyruvate kinase M gene expression. Biochem. Biophys. Res. Commun. 256, 257-262, DOI: 10.1006/bbrc.1999.0228.
• 16. Reinacher M., Eigenbrodt E.: (1981) Immunohistological demonstration of the same type of pyruvate kinase isoenzyme (M2-PK) in tumours of chicken and rat. Virchows Arch. B Cell Pathol. Inci. Mol. Pathol. 37, 79-88.
• 17. Staal G.E.J., Rijksen G.: (1991) Pyruvate kinase in selected human tumours. in: Pretlow T.G., Pretlow T.P., editors, Biochemical and molecular aspects of selected cancers. San Diego: Academic Press, p. 313- 337.
• 18. Noguchi T., Inoue H., Tanaka T.: (1986) The M1 and M2-type isozymes of rat pyruvate kinase are produced from the same gene by alternative splicing. J. Biol. Chem. 261 (29), 13807-13812.
• 19. Dombrauckas JD., Santarsiero B.D., Mesecar A.D.: (2005) Structural basis for tumour pyruvate kinase M2 allosteric regulation and catalysis. Biochemistry 44, 9417-9429, DOI: 10.1021/bi0474923.
• 20. Eigenbrodt E., Reinacher M., Scheefers-Borchel U., Friis R.: (1992) Double role for pyruvate kinase type M2 in the expansion of phosphometabolite pools found in tumour cells. in: Perucho M, editor. Critical Reviews in Oncogenesis, vol. 3. Boca Raton. FL: CRC Press; p. 91-115.
• 21. Mazurek S., Boschek C.B., Hugo F., Eigenbrodt E.: (2005) Pyruvate kinase type M2 and its role in tumour growth and spreading. Semin. Cancer Biol; 15, 300-308, DOI: 10.1016/j.semcancer.2005.04.009.
• 22. Mazurek S., Boschek C.B., Eigenbrodt E.: (1997) The role of phosphometabolites in cell proliferation, energy metabolism, and tumour therapy. J. Bioenerg. Biomembr. 29, 315-330, DOI: 10.1023/A:1022490512705
• 23. Eingebrodt E., Mazurek S., Frus R.R.: (1998) Double role of pyruvate kinase type M2 in the regulation of phosphometabolite pools. In: Cell Growth and Oncogenesis. Bannash P, Kanduc D, Papa S, Tager JM (Eds.) Birkhauser Verlag, Basel, Germany, p. 15-30.
• 24. Mazurek S.: (2011) Pyruvate kinase type M2: A key regulator of the metabolic budget system in tumour cells. Int. J. Biochem. Cell Biol. 43, 969-980, DOI: 10.1016/j.biocel.2010.02.005.
• 25. Ignacak J., Stachurska M.B.:(2003) The dual activity of pyruvate kinase type M2 from chromatin extracts of neoplastic cells. Comp. Biochem. Phys.- B 134, 425-433, DOI: 10.1016/S1096-4959(02)00283-X.
• 26. Ashizawa K., Willingham M.C., Liang C.M., Cheng S.Y.: (1991) In vivo regulation of monomer-tetramer conversion of pyruvate kinase subtype M2 by glucose is mediated via fructose 1,6-bisphosphate. J. Biol. Chem. 266, 16842-16846.
• 27. Struszczyk H.: (1987) Microcrystalline Chitozan. I. Properties and preparation. J. Appl. Polym. Sci. 33, 177-187.
• 28. Capelluto D.G., Kutateladze T.G., Habas R., Finkielstein C.V., He X., Overduin M.: (2002) The DIX domain targets dishevelled to actin stress fibres and vesicular membranes. Nature 419, 726-729, doi:10.1038/nature01056.
• 29. Staal F.J., Noort Mv.M., Strous G.J., Clevers H.C.: (2002) WNT signals are transmitted through Nterminally dephosphorylated beta-catenin. EMBO Rep. 3, 63-68, DOI: 10.1093/embo-reports/kvf002.
• 30. Hurlstone A., Clevers H.: (2002) T-cell factors: turn-ons and turn-offs. EMBO J. 21, 2303-2311, DOI: 10.1093/emboj/21.10.2303.
• 31. Zhou X.P., Waite K.A., Pilarski R., Hampel H., Fernandez M.J., Bos C., Dasouki M., Feldman G.L., Greenberg L.A., Ivanovich J., Matloff E., Patterson A., Pierpont M.E., Russo D., Nassif N.T., Eng C.: (2003) Germline PTEN promoter mutations and deletions in Cowden/Bannayan-Riley-Ruvalcaba syndrome result in aberrant PTEN protein and dysregulation of the phosphoinositol-3-kinase/Akt pathway. Am J. Hum. Genet. 73, 404-411.
• 32. Eng C.: (2003) PTEN one gene, many syndromes. Human Mutation 22, 183-198, DOI: 10.1002/ humu.10257.
• 33. Ignacak J., Wiśniewska-Wrona M., Pałka I., Zagajewski J., Niekraszewicz A.: (2011) Role of chitosan oligomers in regulation of Ehrlich ascites tumour cells proliferation in vitro. In: Jaworska M. (ed.) Progress on Chemistry and Application of Chitin and its Derivatives. Polish Chitin Society, Monograph, vol. XVI, 89-98.
• 34. Ignacak J., Wiśniewska-Wrona M., Pałka I., Niekraszewicz A.: (2013) Role of oligochitosans in regulation of cellular activity and location of pyruvate kinase (PK) isoenzyme M2 that affects proliferation of Ehrlich ascites tumour cells (EAT). In: Jaworska M. (ed.) Progress on Chemistry and Application of Chitin and its Derivatives. Polish Chitin Society, Monograph, vol. XVIII, 67-76.

• Document Type: article