Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1978 Feb;75(2):989–993. doi: 10.1073/pnas.75.2.989

Inhibition of growth and guanylate cyclase activity of an undifferentiated prostate adenocarcinoma by an extract of the balsam pear (Momordica charantia abbreviata).

A J Claflin, D L Vesely, J L Hudson, C B Bagwell, D C Lehotay, T M Lo, M A Fletcher, N L Block, G S Levey
PMCID: PMC411385  PMID: 24847

Abstract

We have recently described the presence of a guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] inhibitor (GCI) in an aqueous extract of the balsam pear (Momordica charantia abbreviata). Because the guanylate cyclase-cyclic GMP system is though to be involved in cell growth, DNA and RNA synthesis, and possible malignant transformation, we examined the effect of the aqueous extract containing GCI on an undifferentiated adenocarcinoma of the rat prostate and concanavalin-A-stimulated [3H]thymidine 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 adencarcinoma 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 GCI. Cyclic GMP levels in the tumor in culture wer 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.

Full text

PDF
989

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. DUNNING W. F. PROSTATE CANCER IN THE RAT. Natl Cancer Inst Monogr. 1963 Oct;12:351–369. [PubMed] [Google Scholar]
  2. DeRubertis F. R., Chayoth R., Field J. B. The content and metabolism of cyclic adenosine 3', 5'-monophosphate and cyclic guanosine 3', 5'-monophosphate in adenocarcinoma of the human colon. J Clin Invest. 1976 Mar;57(3):641–649. doi: 10.1172/JCI108320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. DeRubertis F. R., Craven P. A. Calcium-independent modulation of cyclic GMP and activation of guanylate cyclase by nitrosamines. Science. 1976 Sep 3;193(4256):897–899. doi: 10.1126/science.7837. [DOI] [PubMed] [Google Scholar]
  4. Frandsen E. K., Krishna G. A simple ultrasensitive method for the assay of cyclic AMP and cyclic GMP in tissues. Life Sci. 1976 Mar 1;18(5):529–541. doi: 10.1016/0024-3205(76)90331-3. [DOI] [PubMed] [Google Scholar]
  5. Hadden J. W., Hadden E. M., Haddox M. K., Goldberg N. D. Guanosine 3':5'-cyclic monophosphate: a possible intracellular mediator of mitogenic influences in lymphocytes. Proc Natl Acad Sci U S A. 1972 Oct;69(10):3024–3027. doi: 10.1073/pnas.69.10.3024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Heber-Katz E., Click R. E. Immune responses in vitro. V. Role of mercaptoethanol in the mixed-leukocyte reaction. Cell Immunol. 1972 Nov;5(3):410–418. doi: 10.1016/0008-8749(72)90067-6. [DOI] [PubMed] [Google Scholar]
  7. Kimura H., Mittal C. K., Murad F. Increases in cyclic GMP levels in brain and liver with sodium azide an activator of guanylate cyclase. Nature. 1975 Oct 23;257(5528):700–702. doi: 10.1038/257700a0. [DOI] [PubMed] [Google Scholar]
  8. Kimura H., Murad F. Increased particulate and decreased soluble guanylate cyclase activity in regenerating liver, fetal liver, and hepatoma. Proc Natl Acad Sci U S A. 1975 May;72(5):1965–1969. doi: 10.1073/pnas.72.5.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kram R., Tomkins G. M. Pleiotypic control by cyclic AMP: interaction with cyclic GMP and possible role of microtubules. Proc Natl Acad Sci U S A. 1973 Jun;70(6):1659–1663. doi: 10.1073/pnas.70.6.1659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Krishna G., Krishnan N. A rapid method for the assay of guanylate cyclase. J Cyclic Nucleotide Res. 1975;1(6):293–302. [PubMed] [Google Scholar]
  11. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  12. Miller Z., Lovelace E., Gallo M., Pastan I. Cyclic guanosine monophosphate and cellular growth. Science. 1975 Dec 19;190(4220):1213–1215. doi: 10.1126/science.173021. [DOI] [PubMed] [Google Scholar]
  13. Rudland P. S., Gospodarowicz D., Seifert W. Activation of guanyl cyclase and intracellular cyclic GMP by fibroblast growth factor. Nature. 1974 Aug 30;250(5469):741-2, 773-4. doi: 10.1038/250741a0. [DOI] [PubMed] [Google Scholar]
  14. Seifert W. E., Rudland P. S. Possible involvement of cyclic GMP in growth control of cultured mouse cells. Nature. 1974 Mar 8;248(5444):138–140. doi: 10.1038/248138a0. [DOI] [PubMed] [Google Scholar]
  15. Steiner A. L., Parker C. W., Kipnis D. M. Radioimmunoassay for cyclic nucleotides. I. Preparation of antibodies and iodinated cyclic nucleotides. J Biol Chem. 1972 Feb 25;247(4):1106–1113. [PubMed] [Google Scholar]
  16. Traganos F., Darzynkiewicz Z., Sharpless T., Melamed M. R. Simultaneous staining of ribonucleic and deoxyribonucleic acids in unfixed cells using acridine orange in a flow cytofluorometric system. J Histochem Cytochem. 1977 Jan;25(1):46–56. doi: 10.1177/25.1.64567. [DOI] [PubMed] [Google Scholar]
  17. Vesely D. L., Castro A., Levey G. S. Decreased rat hepatic guanylate cyclase activity in streptozotocin-induced diabetes mellitus. Diabetes. 1977 Apr;26(4):308–313. doi: 10.2337/diab.26.4.308. [DOI] [PubMed] [Google Scholar]
  18. Vesely D. L., Chown J., Levey G. S. Guanylate cyclase activity in fetal, neonatal and adult rat heart. J Mol Cell Cardiol. 1976 Nov;8(11):909–913. doi: 10.1016/0022-2828(76)90073-0. [DOI] [PubMed] [Google Scholar]
  19. Vesely D. L., Graves W. R., Lo T. M., Fletcher M. A., Levey G. S. Isolation of a guanylate cyclase inhibitor from the balsam pear (Momordica charantia abreviata). Biochem Biophys Res Commun. 1977 Aug 22;77(4):1294–1299. doi: 10.1016/s0006-291x(77)80120-4. [DOI] [PubMed] [Google Scholar]
  20. Vesely D. L., Levey G. S. Enhancement of human guanylate cyclase activity by chemical carcinogens. Proc Soc Exp Biol Med. 1977 Jul;155(3):301–304. doi: 10.3181/00379727-155-39794. [DOI] [PubMed] [Google Scholar]
  21. Vesely D. L., Levey G. S. Hydrazine activation of guanylate cyclase: potential application to tobacco carcinogenesis. Biochem Biophys Res Commun. 1977 Jan 24;74(2):780–784. doi: 10.1016/0006-291x(77)90370-9. [DOI] [PubMed] [Google Scholar]
  22. Vesely D. L., Rovere L. E., Levey G. S. Activation of guanylate cyclase by streptozotocin and 1-methyl-1-nitrosourea. Cancer Res. 1977 Jan;37(1):28–31. [PubMed] [Google Scholar]
  23. Watson J., Epstein R., Cohn M. Cyclic nucleotides as intracellular mediators of the expression of antigen-sensitive cells. Nature. 1973 Dec 14;246(5433):405–409. doi: 10.1038/246405a0. [DOI] [PubMed] [Google Scholar]
  24. Weinstein Y., Chambers D. A., Bourne H. R., Melmon K. L. Cyclic GMP stimulates lymphocyte nucleic acid synthesis. Nature. 1974 Sep 27;251(5473):352–353. doi: 10.1038/251352a0. [DOI] [PubMed] [Google Scholar]
  25. Zeilig C. E., Goldberg N. D. Cell-cycle-related changes of 3':5'-cyclic GMP levels in Novikoff hepatoma cells. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1052–1056. doi: 10.1073/pnas.74.3.1052. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES