Research Interests: Analytical Chemistry, Chromatography, Kinetics, Vitamin D, Prostate Cancer, and 16 moreQuantitative analysis, Cell Culture, Cell line, Humans, Male, Plasma, Soybean, High Pressure Liquid Chromatography, Fluorescent Antibody Technique, Quantitative Analysis, Genistein, Mechanism of action, Base Sequence, Hydroxylation, Catabolism, and Biochemistry and cell biology
Research Interests: Vitamin D, Prostate Cancer, Enzyme Inhibitors, Gene expression, Cell Division, and 14 moreHumans, HIstone Deacetylase, Male, High Performance Liquid Chromatography, Enzyme, High Pressure Liquid Chromatography, Time Factors, Enzyme activity, Genistein, Hydroxamic Acids, Phytoestrogens, Estradiol, Biochemistry and cell biology, and Histone deacetylases
Research Interests: Analytical Chemistry, Chromatography, Kinetics, Vitamin D, Prostate Cancer, and 16 moreQuantitative analysis, Cell Culture, Cell line, Humans, Male, Plasma, Soybean, High Pressure Liquid Chromatography, Fluorescent Antibody Technique, Quantitative Analysis, Genistein, Mechanism of action, Base Sequence, Hydroxylation, Catabolism, and Biochemistry and cell biology
1,25 Dihydroxyvitamin D3 (1,25-D3) can be considered an antitumorigenic agent, which can be used in the therapy of malignant diseases such as prostate cancer. In this respect, it is important to note that some prostatic cancer cells... more
1,25 Dihydroxyvitamin D3 (1,25-D3) can be considered an antitumorigenic agent, which can be used in the therapy of malignant diseases such as prostate cancer. In this respect, it is important to note that some prostatic cancer cells express high levels of CYP24, a cytochrome enzyme involved in degradation of 1,25-D3. Genistein, a widely occurring isoflavonoid, inhibits cytochrome enzymes and also exerts antitumorigenic effects. Here, we therefore investigated the effect of genistein on cytochrome enzymes involved in vitamin D metabolism. Treatment of DU-145 prostatic cancer cells with genistein led to a time- and dose-dependent inhibition of CYP24. Additionally CYP27B1 was also inhibited. CYP27B1 is the cytochrome enzyme that synthesizes 1,25-D3. RT-PCR showed that the effect of genistein was mainly due to inhibition of transcription. This often involves the activity of histone deacetylases (HDAC). Thus we tested if the HDAC inhibitor trichostatin A (TSA) reversed the effect of genistein on vitamin D hydroxylases. TSA per se reduced expression of CYP24 mRNA and synergized with genistein to abolish expression after an incubation of 24 h. Importantly, TSA, which itself did not affect CYP27B1 expression, rescued CYP27B1 from transcriptional inhibition by genistein. In conclusion, our data argue for the use of genistein to resensitize prostate cancer cells to 1,25-D3; the addition of TSA may preserve the ability of these cells to synthesize 1,25-D3.
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Research Interests: Nutrition, Sex, Vitamin D, Calcium, Apoptosis, and 13 moreMice, Female, Animals, Male, Cell Death, Risk factors, Calcitriol, Anticancer, Apoptose, Digestive System, Animal models, Risk Factors, and Colon
Research Interests: Vitamin D, Gene expression, Cell Division, Cell line, Cell Differentiation, and 12 moreHumans, Vitamin D receptor, Cellular differentiation, Calcitriol, Clinical Sciences, Epidermal Growth Factor, Carcinoma, Growth Inhibition, Colon Carcinoma, Growth Factor, Caco 2 Cell, and Biochemistry and cell biology
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Although embryonic chick small intestinal segments provide a very limited amount of tissue for preparation of enterocyte brush border membrane vesicles (BBMV), we were able to develop a procedure for isolation of BBMV from cultured... more
Although embryonic chick small intestinal segments provide a very limited amount of tissue for preparation of enterocyte brush border membrane vesicles (BBMV), we were able to develop a procedure for isolation of BBMV from cultured 20-d-old embryonic chick jejunum in high yield by modifying a divalent cation precipitation method. Total yield of the brush border marker enzyme alkaline phosphatase in the vesicle fraction as compared to the crude homogenate was approximately 40%, and the specific activity of the enzyme was increased 25-fold on the average. The brush border membrane vesicle fraction was only contaminated with other cellular organelles (basolateral membranes, mitochondria, lysosomes or endoplasmic reticulum) to a minor extent. Functional integrity of the brush border vesicles was indicated by Na+ gradient-driven electrogenic D-glucose transport leading to concentrative transfer (overshoot) of the sugar into an osmotically active intravesicular space. When jejuna were cul...
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Proper absorption of inorganic phosphate (Pi) from the lumen of the small intestine is of great importance for the achievement of Pi homeostasis. Although due to intralumenal H+ and Pi concentrations, Pi probably can be absorbed as H2PO4-... more
Proper absorption of inorganic phosphate (Pi) from the lumen of the small intestine is of great importance for the achievement of Pi homeostasis. Although due to intralumenal H+ and Pi concentrations, Pi probably can be absorbed as H2PO4- by passive means in the duodenum, transepithelial transport of HPO4(2)- requires uptake from the lumen by an active transport system. The latter has been identified in many species as a Na(+)-Pi cotransport system at the brush-border membrane of the enterocyte. Although it is still a matter of debate whether the intestinal Na+ gradient-driven Pi transport system is electrogenic or electroneutral, there is agreement that the transporter accepts H2PO4- and HPO4(2)- alike. Recently, two laboratories independently isolated a Na(+)-Pi-binding protein which has been tentatively identified as part of the Na(+)-Pi cotransport system. Movement of Pi from the cytosol across the basolateral membrane into the interstitial space has only been preliminarily char...
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Soybean products are highly represented in the traditional Asian diet. Major components of soy proteins are phytoestrogens, such as isoflavones. They may be responsible for the extremely low incidence of prostate and mammary tumors and... more
Soybean products are highly represented in the traditional Asian diet. Major components of soy proteins are phytoestrogens, such as isoflavones. They may be responsible for the extremely low incidence of prostate and mammary tumors and possibly also of colon cancer in countries such as China and Japan. Serum 1,25-dihydroxyvitamin D3 level is inversely related to incidence of some cancers. Levels
Research Interests: Nutrition and Dietetics, Breast Cancer, Food, Vitamin D, Animal Production, and 19 moreMolecular Mechanics, Estrogen Receptor, Humans, Green Tea, Red Wine, Soybean, Risk factors, Antioxidant Activity, Protein kinase B, Colon cancer, Neoplasms, Food Sciences, Risk Factors, Chemical Properties, Biological activity, Cell Survival, Soy Protein, Focal Adhesion Kinase, and Breast Cancer Cells
Soybean,products,are highly represented,in the traditional Asian diet. Major components,of soy proteins are phytoestrogens, such as isoflavones. They may be responsible for the extremely low incidence of... more
Soybean,products,are highly represented,in the traditional Asian diet. Major components,of soy proteins are phytoestrogens, such as isoflavones. They may be responsible for the extremely low incidence of prostate,and,mammary,tumors,and,possibly,also of colon cancer,in countries,such,as China and,Japan. Serum 1,25-dihydroxyvitamin D3 level is inversely related to incidence of some cancers. Levels are determined by skin exposure to ultraviolet light or, to a minor extent,
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Epidemiology suggests that nutritional calcium and vitamin D together prevent colorectal tumor progression. 1,25(OH)2D3 is synthesized and degraded in colonocytes and, when bound to its receptor, has antiproliferative activity.... more
Epidemiology suggests that nutritional calcium and vitamin D together prevent colorectal tumor progression. 1,25(OH)2D3 is synthesized and degraded in colonocytes and, when bound to its receptor, has antiproliferative activity. 1,25(OH)2D3 levels have been successfully measured in cell culture, but this is technically difficult in tissues. Double extraction coupled to an enzyme immunoassay was used to determine 1,25(OH)2D3 concentration in colon mucosa. In a mouse model fed low (0.04%) nutritional calcium, expression of the vitamin D catabolizing CYP24A1, of the synthesizing CYP27B1 hydroxylase and of the vitamin D receptor was induced in the right colon only. While CYP24A1 mRNA was raised in both genders, raised CYP27B1 and VDR was found in females only. Levels of 1,25(OH)2D3 were significantly higher in the right colon of females fed 0.04% calcium compared with the control group on 0.9% calcium, and with males fed either diet. Parallel to increased 1,25(OH)2D3, the intrinsic apopt...
Research Interests: Nutrition, Sex, Vitamin D, Calcium, Apoptosis, and 13 moreMice, Female, Animals, Male, Cell Death, Risk factors, Calcitriol, Anticancer, Apoptose, Digestive System, Animal models, Risk Factors, and Colon
A low vitamin D status and inadequate calcium intake are important risk factors for various types of cancer. Ecological studies using solar UV-B exposure as an index of vitamin D3 photoproduction in the skin found a highly significant... more
A low vitamin D status and inadequate calcium intake are important risk factors for various types of cancer. Ecological studies using solar UV-B exposure as an index of vitamin D3 photoproduction in the skin found a highly significant inverse association between UV-B and mortality in fifteen types of cancer. Of these, colon, rectal, breast, gastric, endometrial, renal and ovarian cancer exhibit a significant inverse relationship between incidence and oral intake of calcium. In addition, lung and endometrial cancer as well as multiple myeloma are considered calcium and vitamin D sensitive. Studies on tissue-specific expression of the CYP27B1-encoded 25-hdroxyvitamin D-1alpha-hydroxylase and of the extracellular calcium-sensing receptor (CaR) have led to an understanding how locally produced 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and extracellular Ca2+ act jointly as key regulators of cellular proliferation, differentiation and function. Thus, impairment of antimitogenic, proapoptotic...
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Extrarenal synthesis of the active vitamin D metabolite 1,25-dihydroxyvitamin-D3 (1,25-D) has been observed in cells derived from human organs prone to sporadic cancer incidence. Enhancement of the synthesizing hydroxylase CYP27B1 and... more
Extrarenal synthesis of the active vitamin D metabolite 1,25-dihydroxyvitamin-D3 (1,25-D) has been observed in cells derived from human organs prone to sporadic cancer incidence. Enhancement of the synthesizing hydroxylase CYP27B1 and reduction of the catabolic CYP24 could support local accumulation of the antimitotic steroid, thus preventing formation of tumors of e.g., colon and breast. By applying quantitative RT-PCR and HPLC it was observed that in colon-(Caco-2) and breast-(MCF-7) derived cells, 17beta-estradiol and genistein induced CYP27B1 but reduced CYP24 activity, while equol was inactive. Mammary cells express both estrogen receptors (ER) a and beta, while colon cells express mainly ERbeta, possibly explaining why MCF-7 cells were more affected. These results indicate a potential, new approach for cancer prevention by counteraction of the 1,25-D-driven negative feedback, i.e., down-regulation of CYP27B1 and up-regulation of CYP24, which prevents its own local accumulation...
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Extensive research on the CYP27B1-encoded 25-(OH)D-1alpha-hydroxylase has contributed much to our understanding about how locally produced 1,25-(OH)2D3 exerts tissue-specific control of cellular growth, differentiation and function.... more
Extensive research on the CYP27B1-encoded 25-(OH)D-1alpha-hydroxylase has contributed much to our understanding about how locally produced 1,25-(OH)2D3 exerts tissue-specific control of cellular growth, differentiation and function. Because many types of epithelial, mesenchymal and immune cells express the 25-(OH)D-1alpha-hydroxylase, many organ functions are necessarily affected by changes in the activity of the enzyme. It is hypothesized that this is likely to occur under conditions of hypovitaminosis D, i.e., at serum 25-(OH)D levels below 30 nM, because extra-renal 25-(OH) D-1alpha-hydroxylase activity is critically limited by the availability of its substrate. This can provide an explanation, on a molecular and cellular basis, for the many observations that significant associations exist between a compromised vitamin D status and the pathogenesis of frequent chronic diseases. In addition to skeletal disorders, vitamin D insufficiency is a risk factor for malignancies, particula...
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Soybean products are highly represented in the traditional Asian diet. Major components of soy proteins are phytoestrogens, such as isoflavones. They may be responsible for the extremely low incidence of prostate and mammary tumors and... more
Soybean products are highly represented in the traditional Asian diet. Major components of soy proteins are phytoestrogens, such as isoflavones. They may be responsible for the extremely low incidence of prostate and mammary tumors and possibly also of colon cancer in countries such as China and Japan. Serum 1,25-dihydroxyvitamin D3 level is inversely related to incidence of some cancers. Levels are determined by skin exposure to ultraviolet light or, to a minor extent, nutritional uptake and by subsequent conversion of the precursor vitamin D to the active hormone by the cytochrome P450 hydroxylases CYP27A1, CYP27B1 (responsible for synthesis) and CYP24 (responsible for catabolism) in liver and kidney. However, vitamin D synthesis is also found in colonocytes and is enhanced during incipient malignancy. This may indicate an autocrine/paracrine role for this differentiation-inducing hormone in defense against progression. We were able to demonstrate that either a single large oral d...
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There is evidence that vitamin D receptor (VDR)-mediated action of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) could limit colon cancer cell growth particularly when induced by activation of the epidermal growth factor receptor... more
There is evidence that vitamin D receptor (VDR)-mediated action of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) could limit colon cancer cell growth particularly when induced by activation of the epidermal growth factor receptor (EGFR). We therefore wanted to ascertain the relevance of this observation for human colon cancerogenesis. Utilizing in situ mRNA hybridization and immunocytochemical techniques, we analyzed cell-specific expression of VDR and EGFR in normal and malignant human colonic mucosa. In normal mucosa, VDR positivity is weak and observed only in a small number of luminal surface colonocytes. In contrast, EGFR expression at a relatively high level is also found in cells at the crypt base. The number of VDR-positive colonocytes increases remarkably during tumor progression. It reaches its maximum in low grade adenocarcinomas and returns to lower levels in highly malignant cancers. In both low- and high grade carcinomas, the great majority of tumor cells contain...
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Using the human colon adenocarcinoma-derived cell line Caco-2, we investigated the possible role of the Ca2+-sensing receptor (CaR) in mediating effects of extracellular Ca2+ on cellular proliferation. Caco-2 cells respond to low ambient... more
Using the human colon adenocarcinoma-derived cell line Caco-2, we investigated the possible role of the Ca2+-sensing receptor (CaR) in mediating effects of extracellular Ca2+ on cellular proliferation. Caco-2 cells respond to low ambient [Ca2+]o by activation of the protein kinase C-signaling pathway, leading to upregulation of c-myc mRNA expression and thereby, finally, to alleviation from the G1/S phase control of the cell cycle. This proliferative response can be reverted by activation of the CaR either through raising [Ca2+]o or, respectively, by using the CaR agonist Gd3+ as a substitute for Ca2+. The inhibitory effect of [Ca2+]o on cell replication exhibits saturation kinetics (IC50 = 0.045 mM), indicating the existence of a highly sensitive CaR operating at low ambient [Ca2+]o. Specific immunostaining revealed the presence of CaR-positive cells in the crypt epithelium of normal human colonic mucosa as well as in glandular (i.e., differentiated structures) of carcinomatous les...
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Epidemiological studies have demonstrated a high incidence of colonic tumors in populations living in areas of low sunlight exposure. This suggests 1,25-dihydroxyvitamin D3, an antimitotic prodifferentiating steroid hormone, as a... more
Epidemiological studies have demonstrated a high incidence of colonic tumors in populations living in areas of low sunlight exposure. This suggests 1,25-dihydroxyvitamin D3, an antimitotic prodifferentiating steroid hormone, as a potentially preventive factor since levels of the precursor 25-hydroxyvitamin D3 in serum are, to a major part, dependent upon sun exposure. Conversion into the active metabolite from the precursor is effected by CYP27B1, and degradation by CYP24. Both p450 hydroxylases are known to be located in the kidney. However, we were able to demonstrate presence, and activity of both enzymes also in the colon. We have shown also that during early tumor progression expression of CYP27B1 and of the vitamin D receptor is upregulated. Therefore the vitamin D system may function as a potent physiological defense against further tumor progression in cancer patients. We suggest that estrogenic substances, and also phytoestrogens present in soy food could, by increasing tumor tissue-located CYP27B1 activity and decreasing degradative CYP24 activity, augment tumor-localized 1,25-dihydroxyvitamin D3 levels and activity.
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Because colorectal cancer (CRC) is a leading cause of cancer mortality in the Western industrialized world, future chemopreventive strategies will be of high socioeconomic importance. Lower CRC incidences in Far Eastern countries in part... more
Because colorectal cancer (CRC) is a leading cause of cancer mortality in the Western industrialized world, future chemopreventive strategies will be of high socioeconomic importance. Lower CRC incidences in Far Eastern countries in part may be attributed to high nutritional intake of soy and its abundance in phytoestrogens. Phytoestrogens are plant-derived substances which, due to molecular similarities to endogenous estrogens, distinctly interact with estrogen receptors ERalpha and ERbeta. Both genomic and nongenomic mechanisms have been shown to be responsible for possible anticarcinogenic properties of phytoestrogens, such as induction of apoptosis and inhibition of tyrosine kinases and DNA topoisomerases. This chapter provides a comprehensive review of a variety of studies exploring possible relations between phytoestrogen uptake and CRC risk. While in vitro and animal studies in general are somewhat supportive of a protective role of phytoestrogens against CRC, epidemiological work so far performed does not allow any conclusion on this issue. Studies about mechanisms of phytoestrogenic action against CRC development have been evaluated as well. Because estrogens, vitamin D, and calcium are frequently suggested to be important in CRC prevention, studies concentrating on interactions of phytoestrogens with these substances have been performed. Although support in evidence for a protective effect of phytoestrogens against CRC has increased over the last decade, it is still too early to give a definite recommendation, especially in view of enduring inconsistencies about concentrations most likely to be effective. Further experimental, and particularly epidemiological, studies are required to advance our understanding of the role of phytoestrogens against colon carcinogenesis.
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Research Interests: Vitamin D, Calcium, Colorectal cancer, Estrogen Receptor, Postmenopausal Women, and 10 moreHumans, Vitamin D receptor, CYP, High Pressure Liquid Chromatography, The Endocrine System Function, Gastrointestinal Tract, Epidemiologic Studies, Tumor Progression, Biochemistry and cell biology, and Gene Expression Regulation
Research Interests: Metabolism, Kinetics, Vitamin D, Cell line, Humans, and 12 moreVitamin D receptor, Calcitriol, High Performance Liquid Chromatography, High Pressure Liquid Chromatography, Caco-2 cells, Digestive System, Side-chain, Oxidation, Enzyme activity, Caco 2 Cell, Biochemistry and cell biology, and Binding affinity
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Research Interests: Western Europe, Multiple sclerosis, Cancer, Vitamin D, Cardiovascular disease, and 17 moreFood Fortification, Metabolic Bone Disease, Humans, Autoimmune Disease, Diabetes mellitus, Europe, Infectious Disease, Congestive Heart Failure, Disease, Diet Therapy, Dietary Supplements, Burden of Disease, Randomized Controlled Trial, Viral Infection, Observational Study, Environment, and Biochemistry and cell biology
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The role of calcifediol in the perception of chronic pain is a widely discussed subject. Low serum levels of calcifediol are especially common in patients with severe pain and fibromyalgia syndrome (FMS). We lack evidence of the role of... more
The role of calcifediol in the perception of chronic pain is a widely discussed subject. Low serum levels of calcifediol are especially common in patients with severe pain and fibromyalgia syndrome (FMS). We lack evidence of the role of vitamin D supplementation in these patients. To our knowledge, no randomized controlled trial has been published on the subject. Thirty women with FMS according to the 1990 and 2010 American College of Rheumatology criteria, with serum calcifediol levels <32ng/ mL (80nmol/L), were randomized to treatment group (TG) or control group (CG). The goal was to achieve serum calcifediol levels between 32 and 48ng/mL for 20weeks via oral supplementation with cholecalciferol. The CG received placebo medication. Re-evaluation was performed in both groups after a further 24weeks without cholecalciferol supplementation. The main hypothesis was that high levels of serum calcifediol should result in a reduction of pain (visual analog scale score). Additional variables were evaluated using the Short Form Health Survey 36, the Hospital Anxiety and Depression Scale, the Fibromyalgia Impact Questionnaire, and the Somatization subscale of Symptom Checklist-90-Revised. A marked reduction in pain was noted over the treatment period in TG: a 2 (groups)×4 (time points) variance analysis showed a significant group effect in visual analog scale scores. This also was correlated with scores on the physical role functioning scale of the Short Form Health Survey 36. Optimization of calcifediol levels in FMS had a positive effect on the perception of pain. This economical therapy with a low side effect profile may well be considered in patients with FMS. However, further studies with larger patient numbers are needed to prove the hypothesis.
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Low nutritional calcium contributes to disruption of the intestinal epithelial barrier function, to hyperproliferation of colonocytes and increased occurrence of aggressive secondary bile acids in the gut lumen. These mechanisms are also... more
Low nutritional calcium contributes to disruption of the intestinal epithelial barrier function, to hyperproliferation of colonocytes and increased occurrence of aggressive secondary bile acids in the gut lumen. These mechanisms are also known to be involved in the etiology of colonic inflammation and cancer. We studied in mice and human adenocarcinoma-derived Caco-2 cells the impact of low calcium on markers of inflammation (cyclooxygenase-2; COX-2), of detoxification (pregnane and xenobiotic receptor (PXR)/steroid and xenobiotic receptor (SXR), cytochrome P450 steroid-inducible 3a11 (CYP3A11)), and on expression of the vitamin D system as a protection against tumorigenesis. Caco-2 cells express high COX-2 and low SXR mRNA levels when subconfluent. During differentiation this is reversed, while low calcium enhanced COX-2 protein expression. In vivo low dietary calcium significantly increased the expression of the PXR target gene CYP3A11 in the proximal colon, suggesting compensatory defense mechanisms. In comparison with males, low nutritional calcium elicits a better protective response in females: both the vitamin D synthesizing 25-hydroxyvitamin D(3 )1alpha hydroxylase (CYP27B1) mRNA and the detoxifying CYP3A11 mRNA are augmented more. While it is recognized that colonic vitamin D synthesis may prevent tumor progression, low dietary calcium also elevates the 1,25-(OH)(2)-D(3) catabolic 25-hydroxyvitamin D(3) 24 hydroxylase (CYP24) expression primarily in the proximal colon. Our data suggest the proximal colon as the primary site of response to insufficient calcium intake.
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There is a growing body of evidence that disturbed circadian clock gene expression is associated with tumor development and tumor progression. Based on our initial experiments demonstrating decreased period 1 (Per1) expression in colon... more
There is a growing body of evidence that disturbed circadian clock gene expression is associated with tumor development and tumor progression. Based on our initial experiments demonstrating decreased period 1 (Per1) expression in colon cancer, we evaluated clock gene and estrogen receptor (ER) alpha/beta expression in colon cancer cells of primary colorectal tumors and adjacent normal colon mucosa (NM) by real-time RT-PCR. Analysis of gene expression in G(2) and G(3) colorectal tumors revealed a decrease of Per1 mRNA compared with paired NM (G(2): 0.52-fold; P = n.s. and G(3): 0.48-fold; P = 0.03). A significant gender specific difference of Per1 expression was observed in G(2) tumors as compared with NM (female: 0.38-fold; P = 0.004 vs. male: 0.73-fold; P = n.s.). Expression of CLOCK was significantly elevated in G(2) tumors of male patients (1.63-fold, P = 0.01). The expression of ER-beta was significantly decreased in G(2) and G(3) tumors (G(2): 0.32-fold; P = 0.003 and 0.27; P = 0.001). No significant gender specific differences of ER-beta reduction in tumors were observed. A significant correlation between the decrease of Per1 and ER-beta in colorectal tumors (r = 0.61; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) was found. No changes in gene expression were detected for ER-alpha and Per2. Our data demonstrate a correlated decrease of Per1 and ER-beta in colorectal tumors, mediated probably by epigenetic mechanisms. The observed gender differences in the expression of CLOCK and Per1 in G(2) tumors might suggest a gender-specific, distinctive role of the cellular clock in colorectal tumorigenesis.
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Epidemiological studies have demonstrated a high incidence of colonic tumors in populations living in areas of low sunlight exposure. This suggests 1,25-dihydroxyvitamin D3, an antimitotic prodifferentiating steroid hormone, as a... more
Epidemiological studies have demonstrated a high incidence of colonic tumors in populations living in areas of low sunlight exposure. This suggests 1,25-dihydroxyvitamin D3, an antimitotic prodifferentiating steroid hormone, as a potentially preventive factor since levels of the precursor 25-hydroxyvitamin D3 in serum are, to a major part, dependent upon sun exposure. Conversion into the active metabolite from the precursor is effected by CYP27B1, and degradation by CYP24. Both p450 hydroxylases are known to be located in the kidney. However, we were able to demonstrate presence, and activity of both enzymes also in the colon. We have shown also that during early tumor progression expression of CYP27B1 and of the vitamin D receptor is upregulated. Therefore the vitamin D system may function as a potent physiological defense against further tumor progression in cancer patients. We suggest that estrogenic substances, and also phytoestrogens present in soy food could, by increasing tumor tissue-located CYP27B1 activity and decreasing degradative CYP24 activity, augment tumor-localized 1,25-dihydroxyvitamin D3 levels and activity.