Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0265264 (HOS)
 1,119 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have shown earlier that 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3] induces cell growth suppression and cell differentiation of a human megakaryoblastic leukemia cell line, HIMeg. However, the molecular mechanism of 1,25(OH)2 D3 action is still unknown. Prompted by this, we have searched here for the presence of 1,25(OH)2 D3 receptor (VDR) expression in HIMeg cells by reverse transcription-polymerase chain reaction (RT-PCR). The amplified product showed an identical size to the product amplified from the control human VDR cDNA and hybridized specifically with the digoxigenin-labeled human VDR cDNA fragment. As expected, VDR mRNA is also expressed in HOS-8603, a human osteosarcoma cell line. These results represent the first reported evidence that VDR mRNA is expressed in megakaryoblastic cells. In addition, the regulation of VDR mRNA expression in HIMeg cells was studied by quantitative RT-PCR. It was found that [correction of the] VDR mRNA expression in HIMeg cells could be down-regulated rapidly by 1,25(OH)2 D3 (10 nM) in a time-dependent manner, reaching a maximal reduction to about 15% of control. However, VDR mRNA expression in HOS-8603 cells was not regulated by 1,25(OH)2 D3 at any time-point tested. Treatment of HIMeg cells with forskolin (1 microM), an activator of adenylate cyclase, caused an increase in VDR mRNA levels. Similarly, VDR mRNA expression in HOS-8603 cells was also up-regulated by forskolin. Consistent with the functionality of the VDR in other target cells, we found that the up-regulation of VDR expression in HIMeg cells by forskolin was accompanied by an increased responsiveness of HIMeg cells to 1,25(OH)2 D3 even though forskolin alone had no effects. Exposure to 1,25(OH)2 D3 in combination with forskolin resulted in a much more significant inhibition of cell proliferation than to 1,25(OH)2 D3 alone. Similarly, forskolin could also augment the differentiation induced by 1,25(OH)2 D3 reflected by a more evident morphological change and a higher percentage of development of cells with multilobular nuclei. These alterations were accompanied by a loss of clonogenic capacity and a decrease in the number of cells in the S phase. These data establish that HIMeg cells express functional VDR, which served to mediate actions of its ligand on the proliferation and differentiation of these cells.
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PMID:Demonstration of vitamin D receptor expression in a human megakaryoblastic leukemia cell line: regulation of vitamin D receptor mRNA expression and responsiveness by forskolin. 863 62

The 14-epimer of MART-10, namely 14-epi-MART-10 (14-epi-2alpha-(3-hydroxypropyl)-1alpha,25-dihydroxy-19-norvitamin D3) and its 2-epimeric analog (14-epi-MART-11) were efficiently synthesized using the Julia coupling reaction to connect between the C5 and C6 positions (steroid numbering). An A-ring precursor was prepared from (-)-quinic acid as shown in the previous MART-10 synthesis. The novel 14-epi-CD-ring coupling partner with an elongated two carbon unit as a sulfone was synthesized from 14-epi-25-hydroxy Grundmann's ketone in good yield. The subsequent coupling reaction followed by a deprotection step afforded a mixture of 14-epi-MART-10 and 14-epi-MART-11 in 40% yield. To separate 14-epi-MART-10 and 14-epi-MART-11, each primary hydroxyl group was esterified with a pivaloyl group and the resulting pivalates 2alpha and 2beta were separated by high performance liquid chromatography. After the separation, the C2-stereochemistry of each (2alpha or 2beta) was determined by 1H NMR (nuclear magnetic resonance) studies including NOE (nuclear Overhauser effect) experiments. The pivaloyl group was removed under basic conditions to obtain the target molecules of 14-epi-MART-10 and 14-epi-MART-11, respectively. The VDR (vitamin D receptor)-binding affinity, HL-60 (human promyelocytic leukemia) cell differentiation activity, antiproliferative activity in PZ-HPV-7 (immortalized normal prostate) cells and transactivation activity of the osteocalcin promoter in HOS (human osteoblast cell line) cells (serum-free conditions) were investigated. In addition, the effects on bone mineral density (BMD) and the blood and urine calcium concentrations of ovariectomized (OVX) rats were examined. 14-epi-MART-10 has much greater antiproliferative and cell differentiation activities compared to 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3).
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PMID:Synthesis and biological activities of 14-epi-MART-10 and 14-epi-MART-11: implications for cancer and osteoporosis treatment. 1966 49

We synthesized and isolated 2 alpha-substituted analogs of 14-epi-previtamin D3 after thermal isomerization at 80 degrees C for the first time. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the 2 alpha-methyl-substituted analog was found to have greater genomic activity than 14-epi-previtamin D3.
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PMID:Synthesis of 2alpha-substituted-14-epi-previtamin D3 and its genomic activity. 1969 43

2beta-substituted analogs of 14-epi-previtamin D(3) were synthesized for the first time by the thermal isomerization of the corresponding 14-epi-vitamin D3 that were available using coupling reaction between the A-ring phosphine oxide derived from a chiral epoxide and CD-ring cis-hydrindanone. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the new analogs were found to be less active, 0.01-0.18% of VDR binding affinity compared with the natural hormone and EC50 1.0-9.1 nM for transactivation activity, than 14-epi-previtamin D3 with 0.5% (VDR) and EC50 0.46 nM, respectively.
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PMID:Synthesis of 2beta-substituted-14-epi-previtamin D3 and testing of its genomic activity. 2021 90