We have recently described the presence of a guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.21 inhibitor (GCI) in an aqueous extract of the balsam pear (Momordica charantia abbreviata). Because the guanylate cyclase-cyclic GMP system is thought to be involved in cell growth, DNA and RNA synthesis, and possibly malignant transformation, we examined the effect of the aqueous extract containing GCI on an undifferentiated adenocarcinoma of the rat prostate and concanavalin-A-stimulated [3Hlthymidine incorporation into cultured splenic lymphocytes, a process thought to be mediated by cyclic GMP. The results demonstrate that the extract of the balsam pear blocks both the growth of the rat prostatic adenocarcinoma in vitro and [3H thymidine incorporation into DNA. DNA histograms from flow cytometry indicated that the extract containing GCI inhibited in the G2 + M phase of the cell cycle, a presumed locus of cyclic GMP effects. In addition, guanylate cyclase activity was significantly greater in the tumor than normal prostate tissue and was decreased by the extract containing GCL Cyclic GMP levels in the tumor in culture were also decreased by addition of the extract. It remains to be determined whether or not the anti-tumor agent and GCI are the same substance.The balsam pear (Momordica charantia abbreviata) is a plant that grows wild throughout subtropical regions of the world, including Florida and the Gulf Coast of the United States; We have recently reported (1) that an aqueous extract of the ripe fruit of the balsam pear contains an inhibitor of guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2], the enzyme that catalyzes the conversion of guanosine triphosphate (GTP) to guanosine 3',5'-monophosphate (cyclic GMP). The guanylate cyclase inhibitor (GCI) blocked both the basal activity of guanylate cyclase and the activation of guanylate cyclase by nitroso chemical carcinogens (1). The latter finding was of particular interest because current evidence suggests that the major role of cyclic GMP in cell biology is concerned with cell growth, DNA and RNA synthesis, and possibly malignant transformation (2-12). A recent investigation by Zeilig and Goldberg (12), using Novikoff rat hepatoma cells, showed that, as these synchronized cells entered mitosis, cellular cyclic GMP levels rose and cellular adenosine 3',5'-monophosphate (cyclic AMP) levels declined. As the cells entered the quiescent stages of growth, the ratios of these nucleotides reversed, with cyclic AMP levels rising and cyclic GMP levels reaching their nadir. It seemed worthwhile, therefore, to determine the effects of the extract on both tumor cells and normal cells.In the present investigation we utilized cell cultures of an undifferentiated adenocarcinoma of the rat prostate, observed MATERIALS AND METHODS Cell Source and Cultivation. The prostatic adenocarcinoma cells in tissue culture were derived from the hormone-responsive G subline of the Dunning R3327 tumor. A subcutaneous G tumor in the 22nd in vivo passag...
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