Purification and Characterization of A Cytostatic Factor With Anti-Viral Activity From The Bitter Melon

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Abstract
A crude aqueous extract of the bitter melon (Momordica charantia) has both cytostatic and cytotoxic activities, and is a competitive inhibitor of guanylate cyclase, activity. This crude preparation kills human leukemic lymphocytes in a dose-dependent manner while not affecting the viability of normal human lymphocytes at these same doses. The purification and characterization of one of these cytostatic factors which also exhibits antiviral activity is described. The partially purified factor was both cytostatic to hamster kidney BHK-21 cells and inhibitory to vesicular stomatitis virus plaque formation in a dose-dependent manner. This preparation was inhibitory to both viral and host cell RNA and protein synthesis as early as 30 min after addition to these samples. As determined by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis this purified factor is a single component with a MW corresponding to 40,000 daltons. The factor is sensitive to boiling and to pretreatments with trypsin, but not RNase or DNase. As determined by radioactive precursor uptake and incorporation studies, the purified factor inhibits both RNA and protein synthesis in intact tissue culture cells and inhibits protein synthesis in a cell-free wheat germ system. DNA synthesis was slightly stimulated. The purified factor is cytostatic for both BHK-21 and for the [human] IM9 leukemic cell lines for at least 120 h. The cytostatic component had no effect on cellular cyclic GMP metabolism.

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