Cancer can be viewed as a disorder generating from an uncoupling of gene expression that controls cellular proliferation and differentiation. Therefore, much attention has been paid to cancer cell lines that can be induced to differentiate after in vitro exposure to chemical or chemotherapeutic agents (for reviews, see refs. 1-3). The K-562 human leukemia cell line provides a useful system for studying human erythroid differentiation because it expresses markers of erythroid lineages, such as hemoglobin.Of the variety of chemotherapeutic agents used in cancer treatment, some can induce cell differentiation (4). In our previous studies we used drugs directed against key enzymes of purine and pyrimidine metabolism (5-7). Activities of target enzymes of these drugs were those that were tightly linked with in vivo and in vitro proliferative activity (5,8,9). The activity of IMP dehydrogenase (IMP:NAD' oxidoreductase; EC 1.1.1.205), the rate-limiting enzyme of de novo GTP biosynthesis, markedly increased in various types of cancer cells; therefore, this enzyme was suggested as a sensitive target for anticancer chemotherapy (5, 10).
Tiazofurin (2-i-D-ribofuranosyl-4-thiazolecarboxamide;NSC-286193) potently inhibits the proliferation ofa variety of experimental and human neoplasms and is now in phase I and II clinical trial (11, 12