cholecalciferol has been researched along with Liver-Neoplasms* in 11 studies
1 review(s) available for cholecalciferol and Liver-Neoplasms
1 trial(s) available for cholecalciferol and Liver-Neoplasms
10 other study(ies) available for cholecalciferol and Liver-Neoplasms
| Article | Year |
|---|---|
Role of vitamin D3 in tumor aggressiveness and radiation response for hepatocellular carcinoma.
Locoregional control is a significant prognostic factor for hepatocellular carcinoma (HCC). Historically, the use of radiotherapy (RT) for HCC was limited owing to the low radiotolerance of the liver and the need for high RT doses for disease control. We aimed to examine if 1α,25-dihydroxyvitamin D3 (calcitriol) has a role in the tumor inhibition and the radiation response of HCC in vitro and in vivo, and explore the underlying mechanisms. The human and murine liver cancer cell lines were selected for cellular and animal experiments to investigate the changes in tumor characteristics and the radiation response after calcitriol supplementation. The effects induced by calcitriol supplementation on interleukin-6 (IL-6) signaling and the tumor immune microenvironment following RT were also examined. Our data revealed that calcitriol supplementation attenuated tumor aggressive behavior, decrease IL-6 expression, and augmented radiation-induced tumor inhibition. The biological changes following calcitriol treatment included suppressed epithelial-mesenchymal transition, attenuated cancer stem cell-like properties and increased radiation-induced reactive oxygen species and cell death in vitro. Regarding immune microenvironment, calcitriol attenuated the recruitment of myeloid-derived suppressor cell (MDSC) recruitment and increased the infiltration of cytotoxic T cells in tumor following RT. Furthermore, When the primary liver tumor was irradiated with larger dose per fraction, calcitriol induced a smaller size of synchronous unirradiated tumor in mice, which linked with attenuated IL-6 signaling and MDSC recruitment. In conclusion, calcitriol treatment reduced tumor aggressiveness and enhanced the radiation response. The inhibited IL-6 signaling and subsequently enhanced antitumor immunity might be responsible to augment radiation-induced tumoricidal effect induced by calcitriol. Based on our results, we suggest that calcitriol could exert the antitumor and radiosensitization effects for HCC, especially for multifocal tumors. Topics: Animals; Calcitriol; Carcinoma, Hepatocellular; Cell Line, Tumor; Cholecalciferol; Interleukin-6; Liver Neoplasms; Mice; Tumor Microenvironment | 2022 |
25-Hydroxyvitamin D Inhibits Hepatitis C Virus Production in Hepatocellular Carcinoma Cell Line by a Vitamin D Receptor-Independent Mechanism.
Previously, we have reported that the active vitamin D metabolite, calcitriol and vitamin D Topics: Calcifediol; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Survival; Cholecalciferol; CRISPR-Cas Systems; Hepacivirus; Humans; Liver Neoplasms; Real-Time Polymerase Chain Reaction; Receptors, Calcitriol; Reverse Transcriptase Polymerase Chain Reaction | 2019 |
Autophagy, apoptosis, vitamin D, and vitamin D receptor in hepatocellular carcinoma associated with hepatitis C virus.
The aims of this study were to investigate the interplay between autophagy and apoptosis and to investigate the association between both of autophagy and apoptosis and vitamin D and its receptor in hepatitis C virus (HCV) viral infection and its implication in the progression into hepatocellular carcinoma (HCC).A cross-sectional study where serum levels of microtubule-associated protein 1A/1B-light chain 3 (LC3); marker of autophagy, caspase-3; marker of apoptosis, vitamin D3 and vitamin D receptor (VDR) were measured in healthy subjects as well as HCV and HCV-HCC patients using enzyme-linked immunosorbent assay technique.Collectively, the liver profile revealed hepatic dysfunctions in HCV patients with or without HCC. A significant reduction in the serum concentration levels LC3 and caspase-3 were observed referring to the down regulation of autophagy and host-mediated apoptosis in HCV patients with or without HCC. Deficiency of vitamin D and decreased levels of its receptor were observed in HCV and HCV-HCC patients.The perturbation in vitamin D/VDR axis, which modulates both of autophagy and apoptosis in HCV infection, may point out to its involvement and implication in the pathogenesis of HCV infection and the development of HCV-related HCC. Therefore, supplementation with vitamin D may not be the only solution to restore the vital biological functions of vitamin D but VDR-targeted therapy may be of great importance in this respect. Topics: Apoptosis; Autophagy; Biomarkers; Carcinoma, Hepatocellular; Caspase 3; Cholecalciferol; Cross-Sectional Studies; Hepacivirus; Hepatitis C; Humans; Liver; Liver Neoplasms; Microtubule-Associated Proteins; Receptors, Calcitriol; Serum Albumin; Vitamin D Deficiency | 2018 |
Hepatitis C infected patients need vitamin D3 supplementation in the era of direct acting antivirals treatment.
It has been reported that the serum level of vitamin D3 (VitD3) could affect the natural course of chronic hepatitis C (CH-C) and the response to treatment with pegylated interferon (Peg-IFN) and ribavirin. Although several mechanisms for the favorable effects of VitD3 supplementation were reported, the total effect of VitD3 supplementation remains unclear. Previously, we reported that supplementation with 1(OH)VitD3 could enhance the Th1 response inducing not only a favorable immune response for viral eradication but also HCC control. Recently, the main treatment of CH-C should be direct acting antivirals (DAAs) without Peg-IFN. Peg-IFN is a strong immune-modulator. Therefore, an immunological analysis should be carried out to understand the effect of VitD3 after treatment of DAAs without Peg-IFN. The induction of a favorable immune response by adding VitD3 might be able to suppress the hepatocarcinogenesis after achieving SVR, especially in children and elderly patients with severe fibrosis lacking sufficient amounts of VitD3. Topics: Antiviral Agents; Carcinoma, Hepatocellular; Cholecalciferol; Dietary Supplements; Hepatitis C; Homeostasis; Humans; Interferon alpha-2; Interferon-alpha; Japan; Liver Cirrhosis; Liver Neoplasms; Polyethylene Glycols; Recombinant Proteins; Th1 Cells | 2017 |
1,25(OH)2D3 inhibits the progression of hepatocellular carcinoma via downregulating HDAC2 and upregulating P21(WAFI/CIP1).
Vitamin D, termed 1,25(OH)2D3 in it's active form, activity is associated with a reduced risk of hepatocellular carcinoma (HCC) and is an important immune regulator. However, the detail molecular mechanisms underlying the effects of 1,25(OH)2D3 on the progression of HCC are widely unknown. Histone deacetwylase 2 (HDAC2) is usually expressed at high levels in tumors, and its downregulation leads to high expression levels of cell cycle components, including p21(WAF1/Cip1), a well-characterized modulator, which is critical in cell senescence and apoptosis. The present study investigated whether vitamin D inhibits HCC via the regulation of HDAC2 and p21(WAF1/Cip1). Firstly, the toxic concentrations of 1,25(OH)2D3 were determined, according to trypan blue and [(3)H]thymidine incorporation assays. Secondly, HCC cells lines were treated with different concentrations of 1,25(OH)2D3. The expression of HDAC2 was either silenced via short hairpin (sh)RNA or induced by transfection of plasmids expressing the HDAC2 gene in certain HCC cells. Finally the mRNA and protein levels of HDAC2 and p21(WAF1/Cip1) were measured using reverse transcription-quantitative polymerase chain reaction and western blot analyses. The results revealed that 1,25(OH)2D3 treatment reduced the expression of HDAC2 and increased the expression of p21(WAF1/Cip1), in a dose-dependent manner, resulting in the reduction of HCC growth. Elevated levels of HDAC2 reduced the expression of p21(WAF1/Cip1), resulting in an increase in HCC growth. HDAC2 shRNA increased the expression of p21(WAF1/Cip1), resulting in reduction in HCC growth. Thus, 1,25(OH)2D3 exerted antitumorigenic effects through decreasing the expression levels of HDAC2 and increasing the expression of p21(WAF1/Cip1), which inhibited the development of HCC and may indicate the possible underlying mechanism. These results suggest that vitamin D3 may be developed as a potential drug for effective therapy in the treatment of HCC. Topics: Blotting, Western; Carcinoma, Hepatocellular; Cell Proliferation; Cell Survival; Cholecalciferol; Cyclin-Dependent Kinase Inhibitor p21; Disease Progression; Down-Regulation; Gene Expression Regulation, Neoplastic; Hep G2 Cells; Humans; Liver Neoplasms; RNA, Messenger; Up-Regulation | 2016 |
Vitamin D: an innate antiviral agent suppressing hepatitis C virus in human hepatocytes.
Vitamin D supplementation was reported to improve the probability of achieving a sustained virological response when combined with antiviral treatment against hepatitis C virus (HCV). Our aim was to determine the in vitro potential of vitamin D to inhibit HCV infectious virus production and explore the mechanism(s) of inhibition. Here we show that vitamin D(3) remarkably inhibits HCV production in Huh7.5 hepatoma cells. These cells express CYP27B1, the gene encoding for the enzyme responsible for the synthesis of the vitamin D hormonally active metabolite, calcitriol. Treatment with vitamin D(3) resulted in calcitriol production and induction of calcitriol target gene CYP24A1, indicating that these cells contain the full machinery for vitamin D metabolism and activity. Notably, treatment with calcitriol resulted in HCV inhibition. Collectively, these findings suggest that vitamin D(3) has an antiviral activity which is mediated by its active metabolite. This antiviral activity involves the induction of the interferon signaling pathway, resulting in expression of interferon-β and the interferon-stimulated gene, MxA. Intriguingly, HCV infection increased calcitriol production by inhibiting CYP24A1 induction, the enzyme responsible for the first step in calcitriol catabolism. Importantly, the combination of vitamin D(3) or calcitriol and interferon-α synergistically inhibited viral production.. This study demonstrates for the first time a direct antiviral effect of vitamin D in an in vitro infectious virus production system. It proposes an interplay between the hepatic vitamin D endocrine system and HCV, suggesting that vitamin D has a role as a natural antiviral mediator. Importantly, our study implies that vitamin D might have an interferon-sparing effect, thus improving antiviral treatment of HCV-infected patients. Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Antiviral Agents; Calcitriol; Carcinoma, Hepatocellular; Cell Line, Tumor; Cholecalciferol; Drug Synergism; Hepacivirus; Hepatitis C, Chronic; Hepatocytes; Humans; Interferon-alpha; Liver Neoplasms; Signal Transduction; Steroid Hydroxylases; Vitamin D3 24-Hydroxylase; Vitamins | 2011 |
19-Nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 (MART-10) is a potent cell growth regulator with enhanced chemotherapeutic potency in liver cancer cells.
The discovery that the active form of vitamin D, 1α,25-dihydroxyvitamin D [1α,25(OH)(2)D] can modulate cellular proliferation and differentiation of cancer cells has led to its potential application as a chemotherapeutic agent to treat a variety of cancers. However, the use of 1α,25(OH)(2)D is limited due to its lethal side effect of hypercalcemia upon systemic administration. To overcome this drawback, numerous analogs have been synthesized. In this report, we examined the anti-proliferative activity of a new analog, 19-nor-2α-(3-hydroxypropyl)-1α,25(OH)(2)D(3) (MART-10), in HepG2 liver cancer cells, and studied the potential mechanisms mediating this action. We found that MART-10 exhibited approximately 100-fold greater activity than 1α,25(OH)(2)D(3) in inhibiting HepG2 cell proliferation as determined by cell number counting method. MART-10 was also approximately 100-fold more potent than 1α,25(OH)(2)D(3) in the upregulation of p21 and p27, that in turn arrested HepG2 cells at the G(0)/G(1) phase to a greater extent. Given that no active caspase 3 was detected and treatment with 1α,25(OH)(2)D(3) or MART-10 did not further increase the fractions of apoptotic and necrosis cells over the controls, the growth-inhibitory effect of 1α,25(OH)(2)D(3) and MART-10 on HepG2 cells may not involve apoptosis. Overall, our findings suggest that MART-10 is a good candidate as a novel therapeutic regimen against liver cancer. Further pre-clinical studies using animal models and the subsequent human clinical trials are warranted. Topics: Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Proliferation; Cholecalciferol; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Gene Expression Regulation, Neoplastic; Hep G2 Cells; Humans; Liver Neoplasms; Vitamin D | 2011 |
Involvement of Vitamin D receptor in the intestinal induction of human ABCB1.
ABCB1 (P-glycoprotein) is an efflux transporter that limits the cellular uptake levels of various drugs in intestine, brain, and other tissues. The expression of human ABCB1 has recently been reported to be under the control of nuclear receptor NR1I subfamily members, pregnane X receptor (PXR, NR1I2) and constitutive androstane receptor (CAR, NR1I3). Here, we have investigated the involvement of another NR1I member, vitamin D receptor (VDR, NR1I1), in ABCB1 expression. In the human colorectal adenocarcinoma cell line LS174T, which abundantly expresses VDR, both 1alpha,25-dihydroxyvitamin D(3) (1,25-VD3) and lithocholic acid (LCA) increased ABCB1 mRNA levels. Reporter gene assays in LS174T cells with constructs containing various lengths of the ABCB1 regulatory region revealed that the region containing multiple nuclear receptor binding motifs located at -7.8 kilobases [termed nuclear receptor-responsive module (NURREM)], to which PXR and CAR also bind, is essential for the VDR-mediated ABCB1 transactivation. Further reporter assays with constructs containing truncated NURREM and gel shift assays suggested simultaneous binding of multiple VDR/retinoid X receptor alpha heterodimers to NURREM. Furthermore, knockdown of VDR expression in LS174T cells blocked the LCA- and the 1,25-VD3-induced transcription of ABCB1 reporter genes. In human hepatoma HepG2 cells, in contrast with LS174T cells, 1,25-VD3 activated the ABCB1 transcription only in the presence of ectopically expressed VDR. These results suggest that the NR1I subfamily members regulate the ABCB1 expression sharing the binding sites within NURREM and that the physiologically produced LCA and 1,25-VD3 may modulate the ABCB1 expression in human intestines, possibly associated with interindividual variations of ABCB1 expression. Topics: Alkaline Phosphatase; Antigens, Neoplasm; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Binding Sites; Cell Line, Tumor; Cholecalciferol; Colonic Neoplasms; Constitutive Androstane Receptor; Electrophoretic Mobility Shift Assay; Genes, Reporter; GPI-Linked Proteins; Humans; Intestinal Mucosa; Intestines; Ligands; Lithocholic Acid; Liver Neoplasms; Protein Multimerization; Receptors, Calcitriol; Regulatory Sequences, Nucleic Acid; Retinoid X Receptor alpha; RNA Interference; RNA, Messenger; Transcriptional Activation; Transfection; Up-Regulation | 2009 |
Plasma carriers influence the uptake of cholecalciferol by human hepatoma-derived cells.
The uptake of [3H]cholecalciferol by the human hepatoma-derived cell lines Hep G2 and Hep 3B was examined as a function of the sterol's presentation on various plasma proteins at their native concentrations. Control cultures utilized devitalized cells cross-linked with glutaraldehyde and estimated nonspecific sterol adherence to cells. With both cell lines, neither albumin nor plasma vitamin D binding protein permitted cholecalciferol uptake above control values. With Hep G2 cells, only low-density lipoprotein presentation of the sterol resulted in significant cellular uptake that had features resembling a receptor-mediated process. With Hep 3B, only high-density lipoprotein presentation of the sterol resulted in a significant uptake that was cell, carrier, and time dependent. These results support the hypothesis that lipoprotein carriers could account for the efficient hepatic accumulation of cholecalciferol in vivo. Topics: Carcinoma, Hepatocellular; Carrier Proteins; Cholecalciferol; Humans; Lipoproteins, HDL; Lipoproteins, LDL; Liver Neoplasms; Tumor Cells, Cultured | 1989 |
25-Hydroxylation of vitamin D3 in the human hepatoma cell lines Hep G2 and Hep 3B.
Two human hepatoma cell lines, Hep G2 and Hep 3B, were screened for vitamin D3-25-hydroxylase enzyme activity by incubation with radioactive vitamin D3. A compound co-chromatographing with 25-OH-D3 was synthesized in both cell lines but its rate of synthesis was tenfold greater in Hep 3B than in Hep G2 cells. The identity of the compound was confirmed by comparing its chromatographic properties with authentic 25-OH-D3 on three different high pressure liquid chromatography systems. Its production was suppressed by adding fetal calf serum (10%), lipoprotein-deficient fetal calf serum, or pure vitamin D-binding globulin to the medium. The mechanism of action of these plasma proteins appears to involve retardation of uptake of the substrate. These two cell lines offer considerable potential as defined in vitro models for studying the effects of physiological factors on the 25-hydroxylation of vitamin D3. Topics: Animals; Carcinoma, Hepatocellular; Cattle; Cholecalciferol; Chromatography, High Pressure Liquid; Estradiol; Humans; Hydroxylation; Lipoproteins; Liver Neoplasms; Mixed Function Oxygenases; Tumor Cells, Cultured | 1988 |