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This study investigated the effects of sinusoidal ELF-MF (1 mT; 50 Hz) on the apoptosis induced by four different compounds, namely vinblastine, etoposide, quercetin, and resveratrol, in human K562 chronic myeloid leukemia cells. The exposure to ELF-MF did not affect growth and viability of untreated K562 cells and did not influence the anti-proliferative effects of resveratrol, vinblastine, and etoposide. On the contrary, in quercetin-treated cells, exposure to ELF-MF significantly reduced the percentage of apoptotic cells and the caspase-3 activity and modified the cell cycle profile especially after 48 h of exposure. In addition, the simultaneous treatments for 24 h with quercetin plus ELF-MF increased Bcl-2 protein expression and prevented quercetin-induced downregulation of Mcl-1 and Bcl-xL. Finally, an increase of HSP70 expression was also observed after prolonged ELF-MF treatment. The ELF-MF-dependent modulation of the expression of anti-apoptotic Bcl-2 family and Hsp70 proteins could act as a pro-survival mechanism in K562 cells.

This work shows that 25 microM quercetin caused a marked inhibition of K562 cells growth together with a mild cytotoxicity, while HSB-2 cells were practically unaffected. Moreover, quercetin induced caspase-3 and cytochrome c-dependent apoptosis almost exclusively in the former cell line. Exposure of K562 cells to quercetin caused also a significant increase of cells in G(2)/M phase that reached the maximum peak at 24 h (4-fold with respect to the basal value). The major sensitivity exhibited by K562 cells was only in part imputable to their higher glutathione content, as compared to HSB-2 cells, thus confirming previous reports describing the formation of intracellular quercetin-thiol toxic adducts in cells exposed to the flavonoid. In fact, after induction of intracellular glutathione increase we detected in both cell lines a significant rise of apoptotic cells, again more marked in K562 cells. By contrast, glutathione-depleted cells, failed to show a decrease of apoptosis in both cell lines, thus contradicting our previous findings and literature data. Since the yet unresolved question about the anti-oxidant or the pro-oxidant capacity of quercetin, we investigated which of these two properties worked in our experimental model. Interestingly, not only quercetin did not produce reactive oxygen species but also prevented their formation, as observed in cells exposed to the oxidizing agent ter-butylhydroperoxide, acting as an efficient oxygen radicals scavenger. This result indicates that quercetin exhibited, in these cell lines, anti-oxidant more than pro-oxidant ability.

In this paper we report that 3'-azido-3'-deoxythymidine (AZT) treatment of human erythroleukemia (K562) cells greatly alters the pattern of protein glycans and significantly modifies beta,(1 --> 4)galactosyltransferase, beta-galactosidase, and alpha,(2 --> 8)sialyltransferase activities. In particular, AZT-treated K562 cells exhibited a decreased incorporation of sialic acid (86% of control) into protein glycans, being the reduced alpha,(2 --> 6) incorporation almost of the same magnitude with respect to that of alpha,(2 --> 3) (93 and 90% of control, respectively). Moreover, the drug exposure of cells induced a decrease of both mannose terminally linked and galactose linked as beta,(1 --> 4) (90 and 92% of control, respectively) and a significant increase of galactose beta,(1 --> 3) (112% of control). In addition, beta,(1 --> 4)galactosyltransferase and beta-galactosidase activities were found enhanced in K562-treated cells (30 and 12%, respectively), while alpha,(2-8 )sialyltransferase activity decreased (75% of control). Sialyltransferase activities of other types i.e. 30, 60, 3 N, 6 N, did not show any appreciable differences irrespective of AZT-treatment. Besides previous studies which report that AZT exposure of K562 cells, indirectly prevents nucleotide-sugar import into the Golgi complex, with consequent inhibition of glycosylation, our observations show for the first time that AZT affects several enzymatic activities involved in specific glycosylation reactions leading, in turn, to protein glycans alteration.