Guanylate cyclase activity in human leukemic and normal lymphocytes. Enzyme inhibition and cytotoxicity of plant extracts.

Cyclic GMP is thought to be involved in lymphocytic cell proliferation and leukemogenesis. In general, the nucleotide is elevated in leukemic vs. normal lymphocytes and changes have been reported to occur during remission and relapse of this disease. Although the cA/cG ratios are higher for normal lymphocytes the basal guanylate cyclase (EC 4.6.1.2) activities do not correlate with altered cyclic GMP levels. The crude guanylate cyclases display classical Michaelis-Menten kinetics with Kms for Mn-GTP of 463 mumol/l and 20-90 mumol/l for normal and leukemic lymphocytes, respectively. An extract from the bitter melon (Momordica charantia) preferentially inhibits the soluble guanylate cyclase from leukemic lymphocytes. This inhibition correlates with its preferential cytotoxic effects for these same cells. Analyses of nine other cytotoxic plant extracts revealed that only an extract from the Lawson's cypress, Chamaecyparis lawsonianna, exhibits comparable cytotoxicity and guanylate cyclase inhibition levels.