The overexpression of this gene determines the resistance of tumor cells to a series of chemotherapeutic drugs
known as multidrug resistance. Many chemotherapeuticals induce both the apoptosis and transcriptional activ-
ity of the MDR1 gene in tumor cells. It is not known, however, how these two processes are associated with
each other. In order to elucidate a possible link between them, we have studied the sphyngomyelinic pathway
of signal transduction. This pathway is activated in response to various stress factors and includes the hydrolysis
of sphyngomyelin of cytoplasmic membrane resulting in an accumulation of intracellular ceramide, which acti-
vates cascades of enzymatic reactions leading to various cell responses, including apoptosis. C2 ceramide
(N
acetyl-D-sphyngosine) and cytosar (1
-D-arabinosylcytosine, or ara C) were used to induce the sphyngo-myelinic pathway. Their effects on human hemoblastosis cell lines (K562 and H9 cell lines) were examined. C2
ceramide and ara C induced apoptosis in both cell lines over an 18-h incubation. C2 ceramide also induced an
increase in the expression of the gene MDR1 in both cell lines, while ara C increased the activity of the gene
MDR1 only in H9 cells. The results obtained provide evidence for the contribution of ceramide-mediated signal
pathway to the control of MDR1 activity.