Effect of zidovudine on the PKC of erythroleukemic K562 and acute lymphoblastic leukemia HSB-2 cells.

""AZT is a drug used for the treatment of HIV-infected patients. In addition to this clinical use, “in vitro” studies have demonstrated that this drug alters some enzymatic activities [1], slows the rate of transferrin receptor endocytosis [2], decreases cell proliferation. Since it is known that PKC is involved in both normal and leukemic hematopoietic cell proliferation and differentiation, we investigated the possible relationship between the PKC activity and its isoforms expression with AZT treatment of human erythroleukemic undifferentiated K562 and acute lymphoblastic leukemia HSB-2 cells. . The cell proliferation was already reduced and AZT caused a significant inhibition of activity at short times in both cells, whereas, a longer exposure (> 24 h) increased the PKC activity. A possible alteration by AZT in the membrane fluidity, was investigated by EPR technique. The zidovudine did not alter the membrane structure in K562 cells, while in the case of HSB-2 caused an increase in the fluidity membrane; this cell line appeared more sensitive to the AZT action on the membrane lipids.. \\tThe PKC α and PKC ßII expression in K562 cells enhanced upon 8 h incubation, but the effect on PKC α was weaker than that measured on PKC ßII. Therefore AZT modifies the PKC activity and expression in both cell lines, but with a different responsiveness.. References. 1. Carnicelli V., Di Giulio A., Bozzi A., Strom R. and Oratore A.: Zidovudine inhibits protein kinase C activity in human chronic myeloid (K562) cells. Basic and Clinical Pharmacology and Toxicology 2006, 99, 317–322.. 2. D'Alessandro AM, D'Andrea G, Di Ciccio L, Brisdelli F, Rinaldi AC, Bozzi A, Oratore A. 3'-Azido-3'-deoxythymidine reduces the rate of transferrin receptor endocytosis in K562 cells.. Biochim Biophys Acta. 1999; 1450(3):232-41.. ""