Abstract
Growth rate inhibition of subcutaneously implanted tumors results from feeding rats and athymic nude mice diets containing 1% cyclocreatine or 1%, 2%, 5%, or 10% creatine. The tumors studied included rat mammary tumors (Ac33tc in Lewis female rats and 13762A in Fischer 344 female rats), rat sarcoma MCI in Lewis male rats, and tumors resulting from the injection of two human neuroblastoma cell lines, IMR-5 and CHP-134, in athymic nude mice. Inhibition was observed regardless of the time experimental diets were administered, either at the time of tumor implantation or after the appearance of palpable tumors. For mammary tumor Ac33tc, the growth inhibition during 24 days after the implantation was approximately 50% for both 1% cyclocreatine and 1% creatine, and inhibition increased as creatine was increased from 2% to 10% of the diet. For the other rat mammary tumor (13762A), there was approximately 35% inhibition by both 1% cyclocreatine and 2% creatine. In the case of the MCI sarcoma, the inhibitory effect appeared more pronounced at earlier periods of growth, ranging from 26% to 41% for 1% cyclocreatine and from 30% to 53% for 1% creatine; there was no significant difference in growth rate between the tumors in the rats fed 1% and 5% creatine. The growth rate of tumors in athymic nude mice, produced by implantation of the human neuroblastoma IMR-5 cell line, appeared somewhat more effectively inhibited by 1% cyclocreatine than by 1% creatine, and 5% creatine feeding was most effective. For the CHP-134 cell line, 33% inhibition was observed for the 1% cyclocreatine diet and 71% for the 5% creatine diet. In several experiments, a delay in appearance of tumors was observed in animals on the experimental diets. In occasional experiments, neither additive inhibited tumor growth rate for the rat tumors or the athymic mouse tumors.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- AIDS conference confused over Thai trial. New Sci. 1992 Sep 12;135(1838):7–7. [PubMed] [Google Scholar]
- Annesley T. M., Walker J. B. Cyclocreatine phosphate as a substitute for creatine phosphate in vertebrate tissues. Energistic considerations. Biochem Biophys Res Commun. 1977 Jan 10;74(1):185–190. doi: 10.1016/0006-291x(77)91392-4. [DOI] [PubMed] [Google Scholar]
- Balaban-Malenbaum G., Gilbert F. Double minute chromosomes and the homogeneously staining regions in chromosomes of a human neuroblastoma cell line. Science. 1977 Nov 18;198(4318):739–741. doi: 10.1126/science.71759. [DOI] [PubMed] [Google Scholar]
- Carney D. N., Zweig M. H., Ihde D. C., Cohen M. H., Makuch R. W., Gazdar A. F. Elevated serum creatine kinase BB levels in patients with small cell lung cancer. Cancer Res. 1984 Nov;44(11):5399–5403. [PubMed] [Google Scholar]
- DeLuca M., Hall N., Rice R., Kaplan N. O. Creatine kinase isozymes in human tumors. Biochem Biophys Res Commun. 1981 Mar 16;99(1):189–195. doi: 10.1016/0006-291x(81)91731-9. [DOI] [PubMed] [Google Scholar]
- Gorsky L. D., Förstermann U., Ishii K., Murad F. Production of an EDRF-like activity in the cytosol of N1E-115 neuroblastoma cells. FASEB J. 1990 Mar;4(5):1494–1500. doi: 10.1096/fasebj.4.5.2155150. [DOI] [PubMed] [Google Scholar]
- Griffiths G. R., Walker J. B. Accumulation of analgo of phosphocreatine in muscle of chicks fed 1-carboxymethyl-2-iminoimidazolidine (cyclocreatine). J Biol Chem. 1976 Apr 10;251(7):2049–2054. [PubMed] [Google Scholar]
- Ishiguro Y., Kato K., Akatsuka H., Ito T. The diagnostic and prognostic value of pretreatment serum creatine kinase BB levels in patients with neuroblastoma. Cancer. 1990 May 1;65(9):2014–2019. doi: 10.1002/1097-0142(19900501)65:9<2014::aid-cncr2820650922>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
- Kaddurah-Daouk R., Lillie J. W., Daouk G. H., Green M. R., Kingston R., Schimmel P. Induction of a cellular enzyme for energy metabolism by transforming domains of adenovirus E1a. Mol Cell Biol. 1990 Apr;10(4):1476–1483. doi: 10.1128/mcb.10.4.1476. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaye A. M., Hallowes R., Cox S., Sluyser M. Hormone-responsive creatine kinase in normal and neoplastic mammary glands. Ann N Y Acad Sci. 1986;464:218–230. doi: 10.1111/j.1749-6632.1986.tb16006.x. [DOI] [PubMed] [Google Scholar]
- Kemp R. G. Inhibition of muscle pyruvate kinase by creatine phosphate. J Biol Chem. 1973 Jun 10;248(11):3963–3967. [PubMed] [Google Scholar]
- Koons S. J., Eckert B. S., Zobel C. R. Immunofluorescence and inhibitor studies on creatine kinase and mitosis. Exp Cell Res. 1982 Aug;140(2):401–409. doi: 10.1016/0014-4827(82)90130-6. [DOI] [PubMed] [Google Scholar]
- Lo K. W., Miller E. E., Morris H. P., Tsou K. C. Chemotherapy of Morris hepatoma 3924A: correlation of size and weight of tumor and preliminary data with 5-fluoro-2'-deoxyuridine (5-FUDR; NSC-27640). Cancer Chemother Rep. 1973 Sep-Oct;57(3):245–249. [PubMed] [Google Scholar]
- LoPresti P., Cohn M. Direct determination of creatine kinase equilibrium constants with creatine or cyclocreatine substrate. Biochim Biophys Acta. 1989 Oct 19;998(3):317–320. doi: 10.1016/0167-4838(89)90291-4. [DOI] [PubMed] [Google Scholar]
- Marletta M. A., Yoon P. S., Iyengar R., Leaf C. D., Wishnok J. S. Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry. 1988 Nov 29;27(24):8706–8711. doi: 10.1021/bi00424a003. [DOI] [PubMed] [Google Scholar]
- McLaughlin A. C., Cohn M., Kenyon G. L. Specificity of creatine kinase for guanidino substrates. Kinetic and proton nuclear magnetic relaxation rate studies. J Biol Chem. 1972 Jul 10;247(13):4382–4388. [PubMed] [Google Scholar]
- Oguchi M., Gerth E., Fitzgerald B., Park J. H. Regulation of glyceraldehyde 3-phosphate dehydrogenase by phosphocreatine and adenosine triphosphate. IV. Factors affecting in vivo control of enzymatic activity. J Biol Chem. 1973 Aug 25;248(16):5571–5576. [PubMed] [Google Scholar]
- Rogers G. W., Miller E. E., Rosato F. E., Rosato E. F. The effect of surgical removal of a rat sarcoma on lymphocyte cytotoxicity. J Surg Oncol. 1977;9(3):307–311. doi: 10.1002/jso.2930090314. [DOI] [PubMed] [Google Scholar]
- Rowley G. L., Greenleaf A. L., Kenyon G. L. On the specificity of creatine kinase. New glycocyamines and glycocyamine analogs related to creatine. J Am Chem Soc. 1971 Oct 20;93(12):5542–5551. doi: 10.1021/ja00750a038. [DOI] [PubMed] [Google Scholar]
- Segaloff A. Hormones and breast cancer. Recent Prog Horm Res. 1966;22:351–379. doi: 10.1016/b978-1-4831-9825-5.50012-9. [DOI] [PubMed] [Google Scholar]
- Shatton J. B., Morris H. P., Weinhouse S. Creatine kinase activity and isozyme composition in normal tissues and neoplasms of rats and mice. Cancer Res. 1979 Feb;39(2 Pt 1):492–501. [PubMed] [Google Scholar]
- Shields R. P., Whitehair C. K. Muscle creatine: in vivo depletion by feeding beta-guanidinopropionic acid. Can J Biochem. 1973 Jul;51(7):1046–1049. doi: 10.1139/o73-136. [DOI] [PubMed] [Google Scholar]
- Storey K. B., Hochachka P. W. Activation of muscle glycolysis: a role for creatine phosphate in phosphofructokinase regulation. FEBS Lett. 1974 Sep 15;46(1):337–339. doi: 10.1016/0014-5793(74)80400-x. [DOI] [PubMed] [Google Scholar]
- Storey K. B., Hochachka P. W. Enzymes of energy metabolism from a vertebrate facultative anaerobe, Pseudemys scripta. Turtle heart phosphofructokinase. J Biol Chem. 1974 Mar 10;249(5):1417–1422. [PubMed] [Google Scholar]
- Tumilowicz J. J., Nichols W. W., Cholon J. J., Greene A. E. Definition of a continuous human cell line derived from neuroblastoma. Cancer Res. 1970 Aug;30(8):2110–2118. [PubMed] [Google Scholar]
- Walker J. B. Creatine: biosynthesis, regulation, and function. Adv Enzymol Relat Areas Mol Biol. 1979;50:177–242. doi: 10.1002/9780470122952.ch4. [DOI] [PubMed] [Google Scholar]
- Walker J. B., Hannan J. K. Creatine biosynthesis during embryonic development. False feedback suppression of liver amidinotransferase by N-acetimidoylsarcosine and 1-carboxymethyl-2-iminoimidazolidine (cyclocreatine). Biochemistry. 1976 Jun 15;15(12):2519–2522. doi: 10.1021/bi00657a004. [DOI] [PubMed] [Google Scholar]
- Walker M. D., Kaye A. M. mRNA for the rat uterine estrogen-induced protein. Translation in vitro and regulation by estrogen. J Biol Chem. 1981 Jan 10;256(1):23–26. [PubMed] [Google Scholar]
- Wang T. Synthesis and properties of N-acetimidoyl derivatives of glycine and sarcosine. J Org Chem. 1974 Nov 29;39(24):3591–3594. doi: 10.1021/jo00938a031. [DOI] [PubMed] [Google Scholar]