Vitamin D3 - better effects if taken alongside isoflavones !?!

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hi, have been reading a bit on D3 in relation to colon cancer, it is saying that isoflavones/phytoestrogens promote D3 in many ways (at least in colon cells that were studied here) and more interestingly, they upregulate expression of vitamin D receptors... makes me wonder if joint D3/genistein supplementation would be worth a trial for kids who do respond on D3 on its own, as it could be due to lack of receptors. or due to presence of these things that degrade D3 to fast, which isoflavones would also help with...NatasaJ Endocrinol. 2006 Nov;191(2):387-98. Phytoestrogens regulate transcription and translation of vitamin D receptor in colon cancer cells.Gilad LA, Faculty

of Agricultural, Food and Environmental Quality Sciences, Institute of

Biochemistry, Food Science and Nutrition, The Hebrew University of

Jerusalem, Rehovot 76100, Israel.The present study assesses the

effects of two isoflavones, genistein and glycitein, and equol - a

product of intestinal bacterial metabolism of dietary isoflavones, on

vitamin D receptor (VDR) expression in an intestinal HT29 cell line.

Genistein and glycitein significantly upregulated the VDR transcription

and translation in HT29 cells. The effect of equol was less pronounced.

Treating HT29 cells transfected with a vector containing the VDR

promoter next to a luciferase reporter with genistein or glycitein

resulted in significant upregulation of VDR promoter activity, in a

manner similar to that induced by 17beta-estradiol (E2). Again, the

effect of equol was less pronounced. VDR luciferase promoter activity

was upregulated most by genistein, then by glycitein and least by equol

when the VDR promoter was cotransfected with estrogen receptor beta.

Reporter gene and chromatin immunoprecipitation (ChIP) assays

demonstrated that E2 upregulates AP-1 and Sp-1 sites present on the VDR

gene. In contrast, the same assays demonstrated that the Sp-1, but not

AP-1, site is induced by the phytoestrogens. Similar to E2, genistein,

glycitein and the isoflavonoid metabolite equol induced higher

concentrations of intracellular free calcium, an event that could

provide the upstream mechanism(s) induced by E2 and phytoestrogens that

initiates the signaling cascade which results in the activation of

extracellular signal-regulated kinase (ERK) signaling pathways and

modulation of Sp-1 sites of the VDR gene, and culminates in enhanced

VDR expression.PMID: 17088408 [PubMed - indexed for MEDLINE]2: Postepy Hig Med Dosw (Online). 2007;61:253-60.[The influence of isoflavonoids on the antitumor activity of vitamin D3] [Article in Polish]Wietrzyk J.Laboratorium

Do´swiadczalnej Terapii Przeciwnowotworowej Instytutu Immunologii i

Terapii Do´swiadczalnej PAN im. L. Hirszfelda we Wroclawiu, Poland.

wietrzyk@...Isoflavonoids exert a regulatory

function on the expression of cytochrome P450 enzymes and also

up-regulate the vitamin D(3) receptor (VDR) on cancer cells, which

increase their sensitivity to 1,25-dihydroxyvitamin D(3) , the

hormonally active form of vitamin D(3) . Isoflavonoids are also able to

raise the serum level of the active form of vitamin D(3) due to their

inhibitory activity on CYP24, the enzyme involved in the degradation of

1,25-dihydroxyvitamin D(3) and its precursor 25-OH-D(3) to inactive

compounds. Another enzyme, CYP27B1, involved in the synthesis of

1,25-dihydroxyvitamin D(3) , is stimulated by isoflavonoids, and this

may result in a similar effect of increasing in the serum level of

1,25-dihydroxyvitamin D3. CYP27B1 and CYP24 were found in kidneys (the

main location of 1,25-(OH) (2)D(3) synthesis) and also in brain cells,

osteoclasts, keratinocytes, macrophages, intestine epithelial cells,

and in some cancer cells. The expression of VDR was detected not only

in the cells primarily targeted by 1,25-dihydroxyvitamin D3, but also

in epithelial and mesenchymal cells. Therefore, combined treatment with

isoflavonoids and 1,25-dihydroxyvitamin D3 might be effective in both

cancer prevention and treatment.Publication Types:English AbstractPMID: 17507873 [PubMed - indexed for MEDLINE]3: J Steroid Biochem Mol Biol. 2003 Feb;84(2-3):149-57. Phytoestrogen regulation of a Vitamin D3 receptor promoter and 1,25-dihydroxyvitamin D3 actions in human breast cancer cells.Wietzke JA, Department of Biological Sciences, University of Notre Dame, IN 46556, USA.1,25-dihydroxyvitamin

D(3) (1,25(OH)(2)D(3)), a steroid hormone derived from Vitamin D(3), is

a negative growth regulator of breast cancer cells, and Vitamin D(3)

analogs represent a novel treatment approach for human cancer.

Elucidation of Vitamin D(3) receptor (VDR) regulation may reveal

strategies to sensitize cancer cells to the effects of

1,25-dihydroxyvitamin D(3) and Vitamin D(3) analogs. We have previously

characterized an estrogen responsive promoter region (800 bp upstream

of exon 1c) in the human VDR gene, and the present studies examined

regulation of this VDR promoter region by two phytoestrogens,

resveratrol (present in red wine) and genistein (present in soy). We

transiently transfected a VDR promoter luciferase construct into the

estrogen receptor (ER) positive human breast cancer cell lines T47D and

MCF-7, and treated with 0.4-4 microM resveratrol or 5-500 nM genistein.

Both phytoestrogens up-regulated the transcription of the VDR promoter,

as measured by reporter gene activity, approximately two-fold compared

to vehicle treated cells. Co-treatment with the anti-estrogen tamoxifen

(TAM) in T47D cells and transfection in an estrogen receptor negative

breast cancer cell line demonstrated that the effects of phytoestrogens

on the VDR promoter are dependent on estrogen receptor. Resveratrol and

genistein also increased VDR protein expression as detected by Western

blotting. Treatment with resveratrol had no effect on cell number or

cell cycle profile, while treatment with genistein increased cell

number. Because resveratrol could up-regulate VDR without increasing

breast cancer cell growth, we hypothesized that resveratrol mediated

increase in VDR expression would sensitize breast cancer cells to the

effects of 1,25-dihydroxyvitamin D(3) and Vitamin D(3) analogs. In

support of this hypothesis, both T47D and MCF-7 cells pre-treated with

resveratrol exhibited increased VDR mediated transactivation of a

Vitamin D(3) responsive promoter compared to cells pre-treated with

vehicle. In addition, co-treatment with resveratrol enhanced the growth

inhibitory effects of 1,25-dihydroxyvitamin D(3) and the Vitamin D(3)

analog EB1089. These data support the concept that dietary factors,

such as phytoestrogens, may impact on breast cancer cell sensitivity to

Vitamin D(3) analogs through regulation of the VDR promoter.Publication Types: PMID: 12710998 [PubMed - indexed for MEDLINE]