cholecalciferol and Endometrial-Neoplasms

The objective of present study was to examine endometrial tissue Be, As, Cr, Mo, Sr, Ti, Tl, Cu, Co, Se, Zn, Mn, Fe, Cd, Pb, Mg, P, erythrocytes CAT, SOD, GSH-Px, GSH, MDA, serum retinol, cholecalciferol, phylloquinone, TSA, LSA, TOS, and TAS status and to evaluate the relationships between the variables. The study had 110 participants; of these, 50 were women with uterine myoma (UM), 10 were women with endometrial cancer (EC), and 50 were healthy female subjects. In the study, vitamin analyses by HPLC and element analyses were determined using ICP-OES method. It was observed that EC group was significantly lower than healthy group in terms of levels of cholecalciferol (p < 0.05), phylloquinone (p < 0.01), GSH (p < 0.05), Fe (p < 0.05), and had a significant rise in Mg/Fe (p < 0.01) and Zn/Fe (p < 0.05) in preoperative period. UM group had significantly lower retinol (p < 0.05), phylloquinone (p < 0.001), GSH-Px (p < 0.01), GSH (p < 0.01), Cr (p < 0.01), Cu (p < 0.05), Mg (p < 0.01), and Zn (p < 0.01) levels than control group in preoperative period and significantly higher levels of MDA (p < 0.01), TSA (p < 0.01), and LSA (p < 0.01) than control group. It was found that significant associations were observed between Cu-CA 15-3 (r = 0.558, p = 0.016), Mn-CA 15-3 (r = 0.511, p = 0.030), P-CA 15-3(r =  - 0.502, p = 0.034) and with UM, also between GSH-CA-125 (r =  - 0.825, p = 0.022) and with EC group. The results of correlation analysis observed that concentrations of Cu, Mn, P, and GSH together with CA 15-3 and CA-125 levels might be important for monitoring patients with UM and EC before surgery.

Topics: Antioxidants; Cholecalciferol; Endometrial Neoplasms; Female; Humans; Male; Myoma; N-Acetylneuraminic Acid; Trace Elements; Vitamin A; Vitamin K 1; Vitamins

Vitamin D (VD) deficiency has been suggested as a risk factor for cancer. One recognized mechanism is that the low-serum 25-hydroxyvitamin D (25(OH)D) of VD deficiency reduces intratumoral 25(OH)D conversion to 1α,25-dihydroxyvitamin D (1,25D, the hormonal form of VD), compromising 1,25D-VD receptor (VDR) antitumoral actions. Reduced tumoral VDR and increased CYP24A1, the enzyme that degrades 1,25D and 25(OH)D, further worsen cancer progression. Importantly, in cells expressing CYP27A1 and/or CYP2R1, which convert inert VD into 25(OH)D, low-serum VD may reduce intratumoral 25(OH)D synthesis thereby compromising VDR antitumoral actions because 25(OH)D can activate the VDR directly and enhance 1,25D-VDR action. Therefore, this study examined whether abnormal endometrial expression of CYP27A1 and/or CYP2R1 may impair VDR-antiproliferative properties in endometrial carcinoma (EC). Immunohistochemical analysis of tissue microarrays of normal human endometrium (NE; n=60) and EC (n=157) showed the expected lower VDR expression in EC (P=0.0002). Instead, CYP24A1 expression was lower in EC compared with NE, while CYP27A1 and CYP2R1 expressions were higher (P=0.0002; P=0.03). Furthermore, in NE and EC, CYP2R1 and CYP27A1 expression correlated directly with nuclear VDR levels, an indicator of ligand-induced VDR activation, and inversely with the proliferation marker Ki67. Accordingly, in the endometrioid carcinoma cell lines IK, RL95/2 and HEC1-A, which express VDR, CYP27A1, and CYP2R1, VD efficaciously reduced cell viability and colony number, with a time course that paralleled actual increases in both intracellular 25(OH)D and nuclear VDR levels. Thus, VD may protect from EC progression in part through increased intratumoral 25(OH)D production by CYP27A1 and CYP2R1 for autocrine/paracrine enhancement of 1,25D-VDR-antiproliferative actions.

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Cell Line, Tumor; Cell Proliferation; Cholecalciferol; Cholestanetriol 26-Monooxygenase; Cytochrome P450 Family 2; Endometrial Neoplasms; Endometrium; Female; Humans; Middle Aged; Receptors, Calcitriol

The possibility that dietary vitamin D(3) (VD(3)) exposure inhibits endometrial carcinogenesis in an animal model and modifies the enhanced risk of endometrial carcinoma associated with obesity was investigated. At 4 weeks of age, Pten(+/-) and wild-type mice were each divided into four treatment groups and fed AIN93G control diet, or AIN93G-based diet containing either 25,000 international units of VD(3) per kilogram of diet, 58% fat to induce obesity (high fat), or high fat and 25,000 international units of VD(3) per kilogram of diet. Mice were kept on these diets until they were sacrificed at week 28. Although VD(3) did not affect endometrial cancer risk, it inhibited obesity-induced increase in endometrial lesions. Specifically, high-fat diet increased focal glandular hyperplasia with atypia and malignant lesions from 58% in the control diet-fed Pten(+/-) mice to 78% in obese mice. Dietary VD(3) decreased the incidence of endometrial pathology in obese Pten(+/-) mice to 25% (P < 0.001). VD(3) altered the endometrial expression of 25-hydroxylase, 1α-hydroxylase, and vitamin D receptor in the wild-type and Pten(+/-) mice. Estrogen receptor-α mRNA levels were higher (P < 0.014) and progesterone receptor protein levels in the luminal epithelium were lower (P < 0.04) in the endometrium of control diet-fed Pten(+/-) than wild-type mice, but the expression of these receptors was not affected by the dietary exposures. VD(3) reversed the obesity-induced increase in osteopontin (P < 0.001) and significantly increased E-cadherin expression (P < 0.019) in the endometrium of obese Pten(+/-) mice. Our data confirm the known association between obesity and endometrial cancer risk. Dietary exposure to VD(3) inhibited the carcinogenic effect of obesity on the endometrium. This protective effect was linked to a reduction in the expression of osteopontin and increase in E-cadherin.

Topics: Animals; Blotting, Western; Bone Density; Cadherins; Cholecalciferol; Diet; Endometrial Neoplasms; Endometrium; Estrogen Receptor alpha; Female; Immunohistochemistry; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Obesity; Osteopontin; Precancerous Conditions; PTEN Phosphohydrolase; Receptors, Progesterone