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. 1997;75(6):850–854. doi: 10.1038/bjc.1997.151

An anti-cancer derivative of butyric acid (pivalyloxmethyl buterate) and daunorubicin cooperatively prolong survival of mice inoculated with monocytic leukaemia cells.

T Kasukabe 1, A Rephaeli 1, Y Honma 1
PMCID: PMC2063395  PMID: 9062406

Abstract

A derivative of butyric acid, pivalyloxymethyl butyrate (AN-9), inhibited the proliferation and induced apoptosis of mouse monocytic leukaemia Mm-A cells, although sodium butyrate, but not AN-9, induced differentiation of the cells. AN-9 and DNA-specific antineoplastic agents synergistically inhibited the growth of Mm-A cells, and the simultaneous treatment was required to evoke the maximum growth-inhibitory effect. On the other hand, there was no synergy between butyrate and the drugs, or AN-9 and anti-metabolic agents in inhibiting the growth of the cells, suggesting that the synergistic effect is specific to AN-9 and DNA-reacting agents. AN-9 as a single agent prolonged the survival of mice inoculated with Mm-A cells in a dose-dependent manner. Moreover, administration of AN-9 plus daunorubicin (DNR) markedly prolonged their survival. These results suggest that combination with AN-9 and DNR entails an obvious therapeutic potential.

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Selected References

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

  1. Aviram A., Zimrah Y., Shaklai M., Nudelman A., Rephaeli A. Comparison between the effect of butyric acid and its prodrug pivaloyloxymethylbutyrate on histones hyperacetylation in an HL-60 leukemic cell line. Int J Cancer. 1994 Mar 15;56(6):906–909. doi: 10.1002/ijc.2910560625. [DOI] [PubMed] [Google Scholar]
  2. Berenbaum M. C. What is synergy? Pharmacol Rev. 1989 Jun;41(2):93–141. [PubMed] [Google Scholar]
  3. Fenaux P., Vanhaesbroucke C., Estienne M. H., Preud'homme C., Pagniez D., Facon T., Millot F., Bauters F. Acute monocytic leukaemia in adults: treatment and prognosis in 99 cases. Br J Haematol. 1990 May;75(1):41–48. doi: 10.1111/j.1365-2141.1990.tb02614.x. [DOI] [PubMed] [Google Scholar]
  4. Honma Y., Fujita Y., Kasukabe T., Hozumi M., Sampi K., Sakurai M., Tsushima S., Nomura H. Induction of differentiation of human acute non-lymphocytic leukemia cells in primary culture by inducers of differentiation of human myeloid leukemia cell line HL-60. Eur J Cancer Clin Oncol. 1983 Feb;19(2):251–261. doi: 10.1016/0277-5379(83)90424-8. [DOI] [PubMed] [Google Scholar]
  5. Honma Y., Honma C., Bloch A. Mechanism of interaction between antineoplastic agents and natural differentiation factors in the induction of human leukemic cell maturation. Cancer Res. 1986 Dec;46(12 Pt 1):6311–6315. [PubMed] [Google Scholar]
  6. Honma Y., Kasukabe T., Hozumi M. Relationship between leukemogenicity and in vivo inducibility of normal differentiation in mouse myeloid leukemia cells. J Natl Cancer Inst. 1978 Sep;61(3):837–841. [PubMed] [Google Scholar]
  7. Kanatani Y., Kasukabe T., Hozumi M., Motoyoshi K., Nagata N., Honma Y. Genistein exhibits preferential cytotoxicity to a leukemogenic variant but induces differentiation of a non-leukemogenic variant of the mouse monocytic leukemia Mm cell line. Leuk Res. 1993 Oct;17(10):847–853. doi: 10.1016/0145-2126(93)90150-j. [DOI] [PubMed] [Google Scholar]
  8. Kasukabe T., Honma Y., Hozumi M. Induction of differentiation of cultured mouse monocytic leukemia cells (Mm-A) by inducers different from those of parent myeloblastic leukemia cells (M1). Jpn J Cancer Res. 1985 Nov;76(11):1056–1063. [PubMed] [Google Scholar]
  9. Kasukabe T., Honma Y., Hozumi M. Selection of mouse macrophage-like sublines that differ in leukemogenic potential and characterization. J Cell Physiol. 1984 Feb;118(2):105–112. doi: 10.1002/jcp.1041180202. [DOI] [PubMed] [Google Scholar]
  10. Lee D. Y., Hayes J. J., Pruss D., Wolffe A. P. A positive role for histone acetylation in transcription factor access to nucleosomal DNA. Cell. 1993 Jan 15;72(1):73–84. doi: 10.1016/0092-8674(93)90051-q. [DOI] [PubMed] [Google Scholar]
  11. Makishima M., Honma Y., Hozumi M., Sampi K., Hattori M., Motoyoshi K. Induction of differentiation of human leukemia cells by inhibitors of myosin light chain kinase. FEBS Lett. 1991 Aug 5;287(1-2):175–177. doi: 10.1016/0014-5793(91)80044-4. [DOI] [PubMed] [Google Scholar]
  12. Miller A. A., Kurschel E., Osieka R., Schmidt C. G. Clinical pharmacology of sodium butyrate in patients with acute leukemia. Eur J Cancer Clin Oncol. 1987 Sep;23(9):1283–1287. doi: 10.1016/0277-5379(87)90109-x. [DOI] [PubMed] [Google Scholar]
  13. Novogrodsky A., Dvir A., Ravid A., Shkolnik T., Stenzel K. H., Rubin A. L., Zaizov R. Effect of polar organic compounds on leukemic cells. Butyrate-induced partial remission of acute myelogenous leukemia in a child. Cancer. 1983 Jan 1;51(1):9–14. doi: 10.1002/1097-0142(19830101)51:1<9::aid-cncr2820510104>3.0.co;2-4. [DOI] [PubMed] [Google Scholar]
  14. Nudelman A., Ruse M., Aviram A., Rabizadeh E., Shaklai M., Zimrah Y., Rephaeli A. Novel anticancer prodrugs of butyric acid. 2. J Med Chem. 1992 Feb 21;35(4):687–694. doi: 10.1021/jm00082a009. [DOI] [PubMed] [Google Scholar]
  15. Okabe-Kado J., Honma Y., Hayashi M., Hozumi M. Effects of transforming growth factor-beta and activin A on vitamin D3-induced monocytic differentiation of myeloid leukemia cells. Anticancer Res. 1991 Jan-Feb;11(1):181–186. [PubMed] [Google Scholar]
  16. Okabe J., Honma Y., Hayashi M., Hozumi M. Actinomycin D restores in vivo sensitivity to differentiation induction of non-differentiating mouse myeloid leukemia cells. Int J Cancer. 1979 Jul 15;24(1):87–91. doi: 10.1002/ijc.2910240115. [DOI] [PubMed] [Google Scholar]
  17. Prasad K. N. Butyric acid: a small fatty acid with diverse biological functions. Life Sci. 1980 Oct 13;27(15):1351–1358. doi: 10.1016/0024-3205(80)90397-5. [DOI] [PubMed] [Google Scholar]
  18. Rabizadeh E., Shaklai M., Nudelman A., Eisenbach L., Rephaeli A. Rapid alteration of c-myc and c-jun expression in leukemic cells induced to differentiate by a butyric acid prodrug. FEBS Lett. 1993 Aug 16;328(3):225–229. doi: 10.1016/0014-5793(93)80932-k. [DOI] [PubMed] [Google Scholar]
  19. Rephaeli A., Rabizadeh E., Aviram A., Shaklai M., Ruse M., Nudelman A. Derivatives of butyric acid as potential anti-neoplastic agents. Int J Cancer. 1991 Aug 19;49(1):66–72. doi: 10.1002/ijc.2910490113. [DOI] [PubMed] [Google Scholar]
  20. Shaw M. T. The distinctive features of acute monocytic leukemia. Am J Hematol. 1978;4(1):97–103. doi: 10.1002/ajh.2830040113. [DOI] [PubMed] [Google Scholar]

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