1, 25(OH)$_2$-23ene-$D_3$ : Effects on Proliferation and Differentiation of U937 Cells in vitro and on Clcium Metabolism of Rat in vivo

1, 25(OH)$_2$-23ene-$D_3$ : in vitro에서 U937 세포의 증식과 분화 및 in vivo에서 쥐의 칼슘대사에 미치는 영향

  • 정수자 (부산여자전문대학 식품영양과) ;
  • 서명자 (부산대학교 식품영양학과)
  • Published : 1995.02.01

Abstract

1, 25(OH)2-23ene-D3 is a novel vitamine D3 analog which has a double bond between C-23 and C-24. We describe the effects of this analog on cell differentiation and cell proliferation in vitro using the human histiocytic lymphoma cell line U937, and on calcium metabolism in rats in vivo. In the present investigation 1, 25(OH)2-23ene-D3 was compared to the natural metabolite of vitamin D3, 1$\alpha$, 25-dihydroxycholecalciferol[1, 25(OH)2-23ene-D3 was more potent than 1, 25(OH)2-23ene-D3 for inhibition of proliferation and induction of differentiation of U937 cells. Especially, its effect on induction of differentiation, as measured by superoxide production and nonspecific esterase(NSE) activity, was about 20-fold more potent that 1, 25(OH)2-23ene-D3. This analog morphologically and functionally differentiated U937 cells to monocyte-macrophage phenotype showing a decrease of N/C ratio in Giemsa staining and the increase of adherence ability to surface. Intraperitoneal administration of 1, 25(OH)2-23ene-D3 to rats showed that the compound had at least 50 times less activity than 1, 25(OH)2-23ene-D3 in causing hypercalcemia and hypercalciuria. The strong direct effects of 1, 25(OH)2-23ene-D3 on cell proliferation and cell differentiation, coupled with its decreased activity of calcium metabolism make this compound an interesting candidate for clinical studies including patients with leukemia, as well as several skin disorders, such as psoriasis.

Keywords

References

  1. Endocrine Rev. v.3 The vitamin endocrine system : steroid metabolism, hormone receptors, and biological response Norman,A.W.;Roth,J.;Orch,L.
  2. Cancer Res. v.42 Presence of 1,25-dihydroxyvitamin D₃receptors in established human cancer cell lines in culture Frampton,R.J.;Suva,L.J.;Eisman,J.A.;Findlay,D.M.;Moore,G.E.;Moseley,J.M.;Martin,T.J.
  3. Science v.221 dihydroxyvitamin D₃receptors in human leukocyte Provvedini,D.M.;Manolagas,S.C.;Deftos,L.J.
  4. Science v.224 1,25-dihydroxyvitamin D₃: a novel immunoregulatory hormone Tsoukas,C.D.;Provvedini,D.M.
  5. J. Immunol. v.135 The effects of 1,25-dihydroxyvitamin D₃on human T lymphocytes activation : a cell cycle analysis Rigby,W.F.C.;Noelle,R.J.;Kraus,K.;Fanger,M.W.
  6. J. Clin. Invest. v.81 1,25-dihydroxyvitamin D₃modulate the expression of a lymphokine posttranscriptionally Tobler,A.;Miller,C.W.;Norman,A.W.;Koeffler,H.P.
  7. J. Immol. v.236 The effect of 1,25-dihydroxyvitamin D₃on in vitro immunoglobulin prodcution in human B cells Iho,S.;Takahashi,T.;Kura,F.;Sugiyama,H.;Hoshino,T.
  8. J. Immunol. v.134 1,25-dihydroxyvitamin D₃supress human T helper/inducer lymphocyte activity in vitro Lemire,J.M.;Adams,J.S.;Kermani Arab,V.;Bakke,A.C.;Sakai,R.;Jordan,S.C.
  9. Bone v.7 1,25-dihydroxyvitamin D₃promotes in vitro morphological and enzymatic changes in normal human monocytes consistent with their differentiation into macrophage Provvedini,D.M.;Deffos,L.T.;Manolagas,S.C.
  10. J. Cell Biol. v.98 1,25-dihydroxyvitamin D₃induced differentiation in a human promyelocytic leukemia cell line(HL-60) : receptor-mediated maturation to macrophage-like cells Mangelsdorf,D.J.;Koeffler,H.P.;Donaldson,C.A.;Pike,J.W.;Haussler,M.R.
  11. Biochem. J. v.204 Alpha,25-dihydroxycholecalciferol and a human myeloid leukemia cell line(HL-60). The presence of a cytosol receptor and induction of differentiation Tanaka,H.;Abe,E.;Miyaura,C.;Kuribayashi,T.;Konno,K.;Nishii,Y.;Suda,T.
  12. Cancer Res. v.43 Induction of differentiation of the human histiolytic lymphoma cell line, U-937 by 1,25-dihydroxyvitamin D₃ Olsson,I.;Gullberg,U.;Ivhed,I.;Nilsson,K.
  13. Pro. Natl. Acad. Sci. v.80 1,25-dihydroxyvitamin D₃and alpha-dihydroxyvitamin D₃prolong survival time of mice inoculated with myeloid leukemia cells Honma,Y.;Hozumi,M.;Abe,E.;Konno,K.;Fukushima,M.
  14. Cancer Res. v.47 Supression of in vivo growth of human cancer solid tumor xenografts by 1α,25-dihydroxyvitamin-D₃ Eisman,J.A.;Barkla,D.H.;Tutton,P.J.
  15. J. Exp. Med. v.138 Antitumor effect of 1α,25-dihydroxyvitamin-D₃ Sato,T.;Takusagawa,K.;Asoo,N.;Konno,K.
  16. Lancet v.337 Topical calcitriol treatment in advanced breast cancer Bower,M.;Colston,K.W.;Stein,R.C.;Hedldy,A.;Gazet,J.C.;Ford,H.T.;Coombes,R.C.
  17. Lancet v.2 Treatment of advanced myelodysplastic syndrome with alfacalciferol Mehta,A.B.;Kumaran,T.D.;Marsh,G.W.
  18. Am. J. Hemat. v.23 Treatment of myelodysplastic syndrome with 1,25-dihydroxyvitamin D₃ Richard,C.;Mazo,E.;Cuadrado,M.A.;Zubizarreta,A.
  19. Br. J. Derm. v.115 An open study of vitamin D₃treatment in psoriasis vulgaris Morimoto,K.;Yoshikawa,Y.;Kozuka,Y.;Kitano,S.;Imanaka,K.;Fukuo,E.K.;Kumahara,Y.
  20. Archs. Biochem. Biophys. v.276 Novel vitamin D₃derivatives, 26-home-${\Delta}^22$-dehydro-1α25(S)-dihydroxyvitamin and 26-homo- -dehydro-1α25(R)-dihydroxyvitamin D₃ Koizumi,T.;Nakao,Y.;Ishizuka,S.;Oshida,J.;Hara,N.;Ikekawa,N.;Fijita,T.
  21. Archs. Biochem. Biophys. v.276 Effects of 1,25-dihydroxyvitamin D₃and its analog in butyrate-induced differentiation of HT-29 human colonic carcinoma cells and on the reversal of the differentiated phenotype Tanaka,Y.;Bush,K.K.;Eguchi,T.;Ikekawa,N.;Taguchi,T.;Kobayashi,Y.;Higgins,P.J.
  22. Kidney Int. Suppl. v.29 New active analogues of vitamin D with low calcemic activity Brown,A.J.;Finch,J.L.;Lopez Hilker,S.;Dusso,A.;Ritter,C.;Pernalete,N.;Slatopolsky,E.
  23. J. Clin. Invest. v.78 Vitamin D Compounds : effect on clonal proliferation and differentiation of human myeloid cell Munker,R.;Norman,A.W.;Koeffler,H.P.
  24. Anal. Biochem. v.20 A multiple-wavelength selector for a continuous spectrophotometric column monitoring system Sarkar,B.C.;Chauhan,U.P.S.
  25. J. Clin. Endocr. Metab. v.57 Specific high-affinity receptors for 1,25-dihydroxyvitamin D₃in human peripheral blood mononuclear cells : presence in monocyte and induction in T lymphocyte following activation Bhalla,A.K.;Amento,E.P.;Clemens,T.L.;Holick,M.F.;Krane,S.M.
  26. Clin. Orth. Rel. Res. v.142 Transport of vitamin d metabolites Haddad,J.G.
  27. A. Rev. Nutr. v.6 Vitamin D receptors : nature and function Haussler,M.R.