Skip to main content
NCBI home page
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
. 1990 May;87(10):3929–3932. doi: 10.1073/pnas.87.10.3929

1,25-Dihydroxy-16-ene-23-yne-vitamin D3 prolongs survival time of leukemic mice.

J Y Zhou 1, A W Norman 1, D L Chen 1, G W Sun 1, M Uskokovic 1, H P Koeffler 1
PMCID: PMC54017  PMID: 2339131

Abstract

The 1,25-dihydroxy-16-ene-23-yne-vitamin D3 [1,25(OH)2-16-ene-23-yne-D3] is a vitamin D analog that is very potent in inhibiting proliferation and inducing differentiation of myeloid leukemic cells in vitro. Also, 1,25(OH)2-16-ene-23-yne-D3 is 300 times less active in mediating intestinal calcium absorption and bone calcium mobilization as compared to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the physiologically active metabolite. Furthermore, 1,25(OH)2-16-ene-23-yne-D3 is 10-25 times less potent than 1,25(OH)2D3 in causing hypercalcemia in BALB/c mice injected intraperitoneally (i.p.) every other day (q.o.d.) for 6 weeks. We explored the therapeutic potential of 1,25(OH)2-16-ene-23-yne-D3 by developing and using the following three leukemia models. (i) Injection of 2.5 x 10(5) myeloid leukemic cells (WEHI 3BD+) into syngeneic BALB/c mice resulted in leukemic death of all diluent-injected mice by day 26. Mice who received the same number of leukemic cells and also received 1,25(OH)2D3 (0.1 micrograms q.o.d., i.p.) had nearly an identical survival curve. Those who received the leukemic cells and 1,25(OH)2-16-ene-23-yne-D3 (1.6 micrograms q.o.d., i.p.) had a significantly (P = 0.003) longer survival, with the last mouse dying of leukemia on day 50. (ii) Injection of 50% fewer leukemic cells (1 x 10(5) cells) into syngeneic BALB/c mice resulted in 86% dead of leukemia at 51 days. Experimental mice who received the same number of leukemic cells and 1,25(OH)2-16-ene-23-yne-D3 (0.8 microgram q.o.d.) had a significantly (P = 0.0006) longer survival than controls; only 53% of the mice were dead by day 100. (iii) After injection of 1.5 x 10(4) leukemic cells, 13% of syngeneic BALB/c mice were free of disease at day 180. In contrast, 43% of mice who received leukemic cells and 1,25(OH)2-16-ene-23-yne-D3 (1.6 micrograms q.o.d.) were still free of disease at day 180. In summary, 1,25(OH)2-16-ene-23-yne-D3 is a vitamin D analog that significantly increased survival of mice who had myeloid leukemia.

Full text

PDF
3929

Selected References

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

  1. Abe E., Miyaura C., Sakagami H., Takeda M., Konno K., Yamazaki T., Yoshiki S., Suda T. Differentiation of mouse myeloid leukemia cells induced by 1 alpha,25-dihydroxyvitamin D3. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4990–4994. doi: 10.1073/pnas.78.8.4990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Honma Y., Hozumi M., Abe E., Konno K., Fukushima M., Hata S., Nishii Y., DeLuca H. F., Suda T. 1 alpha,25-Dihydroxyvitamin D3 and 1 alpha-hydroxyvitamin D3 prolong survival time of mice inoculated with myeloid leukemia cells. Proc Natl Acad Sci U S A. 1983 Jan;80(1):201–204. doi: 10.1073/pnas.80.1.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Koeffler H. P., Hirji K., Itri L. 1,25-Dihydroxyvitamin D3: in vivo and in vitro effects on human preleukemic and leukemic cells. Cancer Treat Rep. 1985 Dec;69(12):1399–1407. [PubMed] [Google Scholar]
  4. Mangelsdorf D. J., Koeffler H. P., Donaldson C. A., Pike J. W., Haussler M. R. 1,25-Dihydroxyvitamin D3-induced differentiation in a human promyelocytic leukemia cell line (HL-60): receptor-mediated maturation to macrophage-like cells. J Cell Biol. 1984 Feb;98(2):391–398. doi: 10.1083/jcb.98.2.391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Munker R., Norman A., Koeffler H. P. Vitamin D compounds. Effect on clonal proliferation and differentiation of human myeloid cells. J Clin Invest. 1986 Aug;78(2):424–430. doi: 10.1172/JCI112593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Reichel H., Koeffler H. P., Norman A. W. The role of the vitamin D endocrine system in health and disease. N Engl J Med. 1989 Apr 13;320(15):980–991. doi: 10.1056/NEJM198904133201506. [DOI] [PubMed] [Google Scholar]
  7. Tanaka H., Abe E., Miyaura C., Kuribayashi T., Konno K., Nishii Y., Suda T. 1 alpha,25-Dihydroxycholecalciferol and a human myeloid leukaemia cell line (HL-60). Biochem J. 1982 Jun 15;204(3):713–719. doi: 10.1042/bj2040713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Warner N. L., Moore M. A., Metcalf D. A transplantable myelomonocytic leukemia in BALB-c mice: cytology, karyotype, and muramidase content. J Natl Cancer Inst. 1969 Oct;43(4):963–982. [PubMed] [Google Scholar]
  9. Zhou J. Y., Norman A. W., Lübbert M., Collins E. D., Uskokovic M. R., Koeffler H. P. Novel vitamin D analogs that modulate leukemic cell growth and differentiation with little effect on either intestinal calcium absorption or bone mobilization. Blood. 1989 Jul;74(1):82–93. [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