EFFECT OF UKRAIN ON HUMAN LYMPHOMA CELL GROWTH WITH DIFFERENT EXPRESSIONS OF HEAT SHOCK PROTEIN 70 (HSP70)
ZHANAEVA S.Y. 1, KOROLENKO T.A.1, SHILOV A.G.2, HALIKOVA T.A.1, GUZHOVA I.V.3, MARGULIS B.A.3, YARYGINA E.S.1
1) Institute of Physiology, Russian Academy of Medical Science, Novosibirsk, Russia.
2) Institute of Cytology and Genetics Russian Academy of Science, Novosibirsk, Russia.
3) Institute of Cytology RAS, St. Petersburg, Russia.
Address for correspondence: T.A. Korolenko, Laboratory of Cellular Biochemistry, Institute of Physiology, Russian Academy of Medical Sciences, ul. Timakova 4, 630117 Novosibirsk, Russia.
Summary: The aim ofthis study was to determine the involvement of heat shock protein 70 (hsp70) in the pro-tective mechanism of U-937 lymphoid cells against Ukrain-induced cell death. We compared the viability and susceptibility of human lymphoid cells U-937 and U-937/hsp70, which differed in their expression of hsp70, to apoptotic Stimuli induced by the anticancer drug Ukrain. Ukrain is known to exhibit high cytotoxic and cytosta-tic activity against malignant, but not normal, cells. Ukrain at concentrations of 34.3, 51.4 and 68.5 muM was shown to decrease the growth rate of U-937 cells by about 3-fold compared with untreated cells, and approxi-mately 55%-65% of the cellpopulation died after 24 h incubation with Ukrain at these concentrations. U-937/hsp70 cells were more resistant to the same concentrations of Ukrain. A lower concentration of Ukrain 6.86 muM induced cell death in about 20% of both U-937 and U-937Ihsp70 cells compared with control, and the mean living cell concentration in both cell types was found to decrease similarly: by 1.3-fold after 48 h incubation, and by 1.7-fold after 72 h. U-937 and U-937Ihsp70 cells both demonstrated susceptibility to apoptosis induced by Ukrain 6.86 muM, whereas Ukrain at a concentration of 3.43 muM was shown to be nontoxic for U-937 and U-937Ihsp70 cells. Treatment of cells with Ukrain at a concentration of 6.86 /muМ for 4 h was followed by de-creased cathepsin В and L activity in both U-937 and U-937Ihsp70 cells. The data presented in this paper indi-cate that hsp70 protected U-937 lymphoid cells from death induced by high concentrations of Ukrain.