Inhibition of angiogenesis as a mechanism for inhibition by L?-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 of colon carcinogenesis induced by azoxymethane in Wistar rats

Abstract

The effects of 1α‐hydroxyvitamin D3[1α(OH)D3] and 1,25‐dihydroxyvitamin D3[1,25(OH)2D3] on the incidence of colon tumors induced by azoxymethane and on the labeling index and angiogenesis of colon tumors were investigated in Wistar rats. Rats received 10 weekly injections of 7.4 mg/kg body weight of azoxymethane and i.p. injections of 1α(OH)D3 and 1,25(OH)2D3 at lower and higher doses every other day for 45 weeks. Prolonged administration of both 1α(OH)D3 and 1,25(OH)2D3 at a higher dose significantly reduced the incidence of colon tumors in week 45. However, administration of 1α(OH)D3 or 1,25(OH)2D3 had little or no effect on the histologic type of colon tumors and cancers. Administration of 1α(OH)D3 and 1,25(OH)2D3 at higher doses significantly decreased the labeling index, the immuno‐histochemical staining for vascular endothelial growth factor and microvessel counts in colon tumors. Our findings suggest that both 1α(OH)D3 and 1,25(OH)2D3 inhibit development of colon tumors. A possible mechanism of inhibition of colon carcinogenesis by 1α(OH)D3 and 1,25(OH)2D3 is the inhibition of angiogenesis as well as an anti‐proliferative effect. Int. J. Cancer 81:730–733, 1999. © 1999 Wiley‐Liss, Inc.

1α,25-Dihydroxyvitamin D3 regulates the expression of Id1 and Id2 genes and the angiogenic phenotype of human colon carcinoma cells

“…1a25(OH) 2 D 3 modulates the angiogenic phenotype of SW480-ADH cells 1a,25(OH) 2 D 3 has been previously shown to block angiogenesis (Iseki et al, 1999). This effect may stem from the modulation of the expression profile of key regulators of vascularization produced by the tumor cells.…”

“…In animal models 1a,25(OH) 2 D 3 treatment causes significant decrease in tumor microvessel density (Iseki et al, 1999;Mantell et al, 2000;Bernardi et al, 2002). The effect of 1a,25(OH) 2 D 3 on tumor angiogenesis is a sum of hormone-induced changes in the angiogenic profile of tumor cells and direct 1a,25(OH) 2 D 3 effects on endothelial cells.…”

“…1a,25-Dihydroxyvitamin D 3 (1a,25(OH) 2 D 3 ) induces growth arrest and differentiation of colon cancer cells (Diaz et al, 2000;Palmer et al, 2001) and has antitumor, antimetastic (Evans et al, 2000;Koli and Keski-Oja, 2000) and antiangiogenic (Iseki et al, 1999) effects in vitro and in animal models of colorectal cancer. Several nonhypercalcemic 1a,25(OH) 2 D 3 derivatives have recently entered clinical trials in patients with colorectal carcinomas and other neoplasms (Gross et al, 1998;Gulliford et al, 1998;Smith et al, 1999;Dalhoff et al, 2003).…”

Reconsidering the connection between vitamin D levels and age-related macular degeneration

“…Furthermore, it was recently shown that vitamin D was a potent inhibitor of angiogenesis by its effects on endothelial cells 34 and by interrupting signaling pathways that are key to angiogenesis, specifically in tumorigenesis. 35,36 The primary purpose of this study was to examine the relationship between serum vitamin D levels and AMD. We hypothesized that individuals in the highest quintile of serum vitamin D levels would have a lower prevalence of AMD compared with those in the lowest quintile.…”

Relationships of uPA and VEGF Expression in Esophageal Cancer and Microvascular Density with Tumorous Invasion and Metastasis

“…Tissue sections showed that granules of blown yellow to blow color present in cytoplasm were positive markers. In terms of Iseki K criteria (Iseki et al, 1999), an comprehensive assessment was conducted according to the staining intensity and the number of positive cells and converted into the positive index: a staining intensity (0=none, 1=weak, 2= moderate, 3= strong); b number of positive cells (0=0 to 5% positive staining cells, 1=5% to 50% positive staining cells, 2=50% to 100% positive staining cells). If the total score of a and b was 0 to 1, the positive index was 0; If the total score of a and b was 2, the positive index was 1; If the total score of a and b was 3, the positive index was 2; If the total score of a and b was 4 or 5, the positive index was 3.…”