© 2000 American Heart Association, Inc.
Cellular Biology |
1
,25-Dihydroxyvitamin D3 Inhibits Angiogenesis In Vitro and In Vivo
From the Wellcome Trust Centre for Cell Matrix Research, Department of Medicine (D.J.M., P.E.O., E.B.M., A.E.C.) and Surgery (N.J.B.), University of Manchester, Manchester, UK.
Abstract—Modulation of
angiogenesis is now a recognized strategy for the prevention and
treatment of pathologies categorized by their reliance on a vascular
supply. The purpose of this study was to evaluate the effect of
1
,25-dihydroxyvitamin D3
[1,25(OH)2D3], the active metabolite of
vitamin D3, on angiogenesis by using well-characterized in
vitro and in vivo model systems. 1,25(OH)2D3
(1x10-9 to 1x10-7
mol/L) significantly inhibited vascular endothelial
growth factor (VEGF)-induced endothelial cell sprouting
and elongation in vitro in a dose-dependent manner and had a small, but
significant, inhibitory effect on VEGF-induced
endothelial cell proliferation.
1,25(OH)2D3 also inhibited the formation of
networks of elongated endothelial cells within 3D
collagen gels. The addition of 1,25(OH)2D3 to
endothelial cell cultures containing sprouting
elongated cells induced the regression of these cells, in the absence
of any effect on cells present in the cobblestone monolayer.
Analysis of nuclear morphology, DNA integrity, and enzymatic in
situ labeling of apoptosis-induced strand breaks demonstrated
that this regression was due to the induction of apoptosis
specifically within the sprouting cell population. The effect of
1,25(OH)2D3 on angiogenesis in vivo was
investigated by using a model in which MCF-7 breast carcinoma cells,
which had been induced to overexpress VEGF, were xenografted
subcutaneously together with MDA-435S breast carcinoma cells into nude
mice. Treatment with 1,25(OH)2D3 (12.5 pmol/d
for 8 weeks) produced tumors that were less well vascularized than
tumors formed in mice treated with vehicle alone. These results
highlight the potential use of 1,25(OH)2D3 in
both the prevention and regression of conditions characterized by
pathological angiogenesis.
Key Words: endothelium • angiogenesis • apoptosis • vitamin D3 • growth factors
This article has been cited by other articles:
 |
|
 |
|
  M. F. Holick Vitamin D and Sunlight: Strategies for Cancer Prevention and Other Health Benefits Clin. J. Am. Soc. Nephrol., September 1, 2008; 3(5): 1548 - 1554. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Hsu, Y. Tintut, and L. L. Demer Vitamin D and Osteogenic Differentiation in the Artery Wall Clin. J. Am. Soc. Nephrol., September 1, 2008; 3(5): 1542 - 1547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Rossi, J. K. McLaughlin, P. Lagiou, C. Bosetti, R. Talamini, L. Lipworth, A. Giacosa, M. Montella, S. Franceschi, E. Negri, et al. Vitamin D intake and breast cancer risk: a case-control study in Italy Ann. Onc., August 18, 2008; (2008) mdn550v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Myrthue, B. L.S. Rademacher, J. Pittsenbarger, B. Kutyba-Brooks, M. Gantner, D. Z. Qian, and T. M. Beer The Iroquois Homeobox Gene 5 Is Regulated by 1,25-Dihydroxyvitamin D3 in Human Prostate Cancer and Regulates Apoptosis and the Cell Cycle in LNCaP Prostate Cancer Cells Clin. Cancer Res., June 1, 2008; 14(11): 3562 - 3570. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Talmor, E. Golan, S. Benchetrit, J. Bernheim, O. Klein, J. Green, and G. Rashid Calcitriol blunts the deleterious impact of advanced glycation end products on endothelial cells Am J Physiol Renal Physiol, May 1, 2008; 294(5): F1059 - F1064. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F Holick and T. C Chen Vitamin D deficiency: a worldwide problem with health consequences Am. J. Clinical Nutrition, April 1, 2008; 87(4): 1080S - 1086S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Tsuzuki and Y. Kawakami Tumor angiogenesis suppression by {alpha}-eleostearic acid, a linolenic acid isomer with a conjugated triene system, via peroxisome proliferator-activated receptor {gamma} Carcinogenesis, April 1, 2008; 29(4): 797 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Valrance, A. H. Brunet, and J. Welsh Vitamin D Receptor-Dependent Inhibition of Mammary Tumor Growth by EB1089 and Ultraviolet Radiation in Vivo Endocrinology, October 1, 2007; 148(10): 4887 - 4894. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Nakagawa, A. Shibata, S. Yamashita, T. Tsuzuki, J. Kariya, S. Oikawa, and T. Miyazawa In Vivo Angiogenesis Is Suppressed by Unsaturated Vitamin E, Tocotrienol J. Nutr., August 1, 2007; 137(8): 1938 - 1943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. Holick Vitamin D Deficiency N. Engl. J. Med., July 19, 2007; 357(3): 266 - 281. [Full Text] [PDF]
|
|
|
|
 |
|
 G. E. Mullin and A. Dobs Vitamin D and Its Role in Cancer and Immunity: A Prescription for Sunlight Nutr Clin Pract, June 1, 2007; 22(3): 305 - 322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Albert, E. A. Scheef, S. Wang, F. Mehraein, S. R. Darjatmoko, C. M. Sorenson, and N. Sheibani Calcitriol Is a Potent Inhibitor of Retinal Neovascularization Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 2327 - 2334. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ben-Shoshan, S. Amir, D. T. Dang, L. H. Dang, Y. Weisman, and N. J. Mabjeesh 1{alpha},25-dihydroxyvitamin D3 (Calcitriol) inhibits hypoxia-inducible factor-1/vascular endothelial growth factor pathway in human cancer cells Mol. Cancer Ther., April 1, 2007; 6(4): 1433 - 1439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Chung, A. R. Karpf, J. R. Muindi, J. M. Conroy, N. J. Nowak, C. S. Johnson, and D. L. Trump Epigenetic Silencing of CYP24 in Tumor-derived Endothelial Cells Contributes to Selective Growth Inhibition by Calcitriol J. Biol. Chem., March 23, 2007; 282(12): 8704 - 8714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Tsuzuki, A. Shibata, Y. Kawakami, K. Nakagawa, and T. Miyazawa Conjugated Eicosapentaenoic Acid Inhibits Vascular Endothelial Growth Factor-Induced Angiogenesis by Suppressing the Migration of Human Umbilical Vein Endothelial Cells J. Nutr., March 1, 2007; 137(3): 641 - 646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-Y. Bao, J. Yao, and Y.-F. Lee 1{alpha}, 25-dihydroxyvitamin D3 suppresses interleukin-8-mediated prostate cancer cell angiogenesis Carcinogenesis, September 1, 2006; 27(9): 1883 - 1893. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Cui and T. E. Rohan Vitamin d, calcium, and breast cancer risk: a review. Cancer Epidemiol. Biomarkers Prev., August 1, 2006; 15(8): 1427 - 1437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Masuda and G. Jones Promise of vitamin D analogues in the treatment of hyperproliferative conditions. Mol. Cancer Ther., April 1, 2006; 5(4): 797 - 808. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. F. Garland, F. C. Garland, E. D. Gorham, M. Lipkin, H. Newmark, S. B. Mohr, and M. F. Holick The Role of Vitamin D in Cancer Prevention Am J Public Health, February 1, 2006; 96(2): 252 - 261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-Y. Bao, S.-D. Yeh, and Y.-F. Lee 1{alpha},25-dihydroxyvitamin D3 inhibits prostate cancer cell invasion via modulation of selective proteases Carcinogenesis, January 1, 2006; 27(1): 32 - 42. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nagpal, S. Na, and R. Rathnachalam Noncalcemic Actions of Vitamin D Receptor Ligands Endocr. Rev., August 1, 2005; 26(5): 662 - 687. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Taverna, J.-L. Selam, and G. Slama Association between a Protein Polymorphism in the Start Codon of the Vitamin D Receptor Gene and Severe Diabetic Retinopathy in C-Peptide-Negative Type 1 Diabetes J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4803 - 4808. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nakagawa, Y. Sasaki, S. Kato, N. Kubodera, and T. Okano 22-Oxa-1{alpha},25-dihydroxyvitamin D3 inhibits metastasis and angiogenesis in lung cancer Carcinogenesis, June 1, 2005; 26(6): 1044 - 1054. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Bachschmid and B. van der Loo A New "Sunshine" in the Vasculature? Circulation, April 5, 2005; 111(13): 1571 - 1573. [Full Text] [PDF]
|
|
|
|
|
|
D. Somjen, Y. Weisman, F. Kohen, B. Gayer, R. Limor, O. Sharon, N. Jaccard, E. Knoll, and N. Stern 25-Hydroxyvitamin D3-1{alpha}-Hydroxylase Is Expressed in Human Vascular Smooth Muscle Cells and Is Upregulated by Parathyroid Hormone and Estrogenic Compounds Circulation, April 5, 2005; 111(13): 1666 - 1671. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nakagawa, A. Kawaura, S. Kato, E. Takeda, and T. Okano 1{alpha},25-Dihydroxyvitamin D3 is a preventive factor in the metastasis of lung cancer Carcinogenesis, February 1, 2005; 26(2): 429 - 440. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.E. Norman and J.T. Powell Vitamin D, Shedding Light on the Development of Disease in Peripheral Arteries Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 39 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zhang, F. Jiang, P. Li, C. Li, Q. Ma, S. V. Nicosia, and W. Bai Growth Suppression of Ovarian Cancer Xenografts in Nude Mice by Vitamin D Analogue EB1089 Clin. Cancer Res., January 1, 2005; 11(1): 323 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Farrington-Rock, N.J. Crofts, M.J. Doherty, B.A. Ashton, C. Griffin-Jones, and A.E. Canfield Chondrogenic and Adipogenic Potential of Microvascular Pericytes Circulation, October 12, 2004; 110(15): 2226 - 2232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Levine and D. Teegarden 1{alpha},25-Dihydroxycholecalciferol Increases the Expression of Vascular Endothelial Growth Factor in C3H10T1/2 Mouse Embryo Fibroblasts J. Nutr., September 1, 2004; 134(9): 2244 - 2250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. V. Stewart and N. L. Weigel Vitamin D and Prostate Cancer Experimental Biology and Medicine, April 1, 2004; 229(4): 277 - 284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Beer and A. Myrthue Calcitriol in cancer treatment: From the lab to the clinic Mol. Cancer Ther., March 1, 2004; 3(3): 373 - 381. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. C. Villablanca, K. A. Lewis, D. Tham, and J. C. Rutledge Differential regulation of gene expression by ovariectomy in mouse aorta Physiol Genomics, February 6, 2003; 12(3): 175 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Beer, K. M. Eilers, M. Garzotto, M. J. Egorin, B. A. Lowe, and W. D. Henner Weekly High-Dose Calcitriol and Docetaxel in Metastatic Androgen-Independent Prostate Cancer J. Clin. Oncol., January 1, 2003; 21(1): 123 - 128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kanda, Y. Mochizuki, Y. Miyata, H. Kanetake, and N. Yamamoto Effects of Vitamin D3-Binding Protein-Derived Macrophage Activating Factor (GcMAF) on Angiogenesis J Natl Cancer Inst, September 4, 2002; 94(17): 1311 - 1319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Bernardi, C. S. Johnson, R. A. Modzelewski, and D. L. Trump Antiproliferative Effects of 1{alpha},25-Dihydroxyvitamin D3 and Vitamin D Analogs on Tumor-Derived Endothelial Cells Endocrinology, July 1, 2002; 143(7): 2508 - 2514. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D M Freedman, M Dosemeci, and K McGlynn Sunlight and mortality from breast, ovarian, colon, prostate, and non-melanoma skin cancer: a composite death certificate based case-control study Occup. Environ. Med., April 1, 2002; 59(4): 257 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Zehnder, R. Bland, R. S. Chana, D. C. Wheeler, A. J. Howie, M. C. Williams, P. M. Stewart, and M. Hewison Synthesis of 1,25-Dihydroxyvitamin D3 by Human Endothelial Cells Is Regulated by Inflammatory Cytokines: A Novel Autocrine Determinant of Vascular Cell Adhesion J. Am. Soc. Nephrol., March 1, 2002; 13(3): 621 - 629. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. TOSETTI, N. FERRARI, S. DE FLORA, and A. ALBINI Angioprevention': angiogenesis is a common and key target for cancer chemopreventive agents FASEB J, January 1, 2002; 16(1): 2 - 14. [Abstract] [Full Text] [PDF]
|
|