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| 1 | CYP24A1 inhibition facilitates the anti-tumor effect of vitamin D3 on colorectal cancer cells显示文摘AIM:The effects of vitamin D3 have been investigated on various tumors, including colorectal cancer (CRC). 25-hydroxyvitamin-D3-24-hydroxylase (CYP24A1), the enzyme that inactivates the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 (1,25-D3), is considered to be the main enzyme determining the biological halflife of 1,25-D3. During colorectal carcinogenesis, the expression and concentration of CYP24A1 increases significantly, suggesting that this phenomenon could be responsible for the proposed efficacy of 1,25-D3 in the treatment of CRC. The aim of this study was to investigate the anti-tumor effects of vitamin D3 on the human CRC cell line Caco-2 after inhibition of the cytochrome P450 component of CYP24A1 activity. METHODS:We examined the expression of CYP24A1 mRNA and the effects of 1,25-D3 on the cell line Caco-2 after inhibition of CYP24A1. Cell viability and proliferation were determined by means of sulforhodamine-B staining and bromodeoxyuridine incorporation, respectively, while cytotoxicity was estimated via the lactate dehydrogenase content of the cell culture supernatant. CYP24A1 expression was measured by realtime reverse transcription polymerase chain reaction. A number of tetralone compounds were synthesized to investigate their CP24A1 inhibitory activity. RESULTS:In response to 1,25-D3, CYP24A1 mRNA expression was enhanced significantly, in a time- and dose-dependent manner. Caco-2 cell viability and proliferation were not influenced by the administration of 1,25-D3 alone, but were markedly reduced by coadministration of 1,25-D3 and KD-35, a CYP24A1-inhibiting tetralone. Our data suggest that the mechanism of action of co-administered KD-35 and 1,25-D3 does not involve a direct cytotoxic effect, but rather the inhibition of cell proliferation. CONCLUSION:These findings demonstrate that the selective inhibition of CYP24A1 by compounds such as KD-35 may be a new approach for enhancement of the anti-tumor effect of 1,25-D3 on CRC. | János P Kósa Péter Horváth János Wlfling Dóra Kovács Bernadett Balla Péter Mátyus Evelin Horváth Gábor Speer István Takács Zsolt Nagy Henrik Horváth Péter Lakatos | 2013 | World Journal of Gastroenterology2013，19，17： | 5 |
| 2 | Effects of locally applied vascular endothelial growth factor and VEGF-inhibitor to the rabbit tibia during distraction osteogenesis显示文摘 | Henrik E Kristian G Bundgaard M | 2003 | J Orthop Res2003，21，： | 1 |
| 3 | Increased blastocyst formation of cloned porcine embryos produced with donor cells pre-treated with Xenopus egg extract and/or digitonin显示文摘 | Ying Liu Olga ?strup Juan Li Gábor Vajta Lin Lin Peter M. Kragh Stig Purup Poul Hyttel Henrik Callesen | 2011 | Zygote2011，，1： | 1 |
| 4 | Oxalate production by Sclero- tinia sclerotiorum deregulates guard ceils during infection 显示文摘 | REJANE L G HENRIK U S | 2004 | Plant Physiology2004，136，： | 1 |
| 5 | Top-tier base oil trends reflect European engine oil demands显示文摘 | Matti L Henrik G H | 2000 | Lubricant World2000，10，11： | 1 |
| 6 | Crystal structure of the human urokinase plasminogen activator receptor bound to an antagonist peptide 显示文摘 | Paola L Marie HLD Henrik G | 2005 | The EMBO Journal2005，24，： | 1 |
| 7 | Production of a healthy calf by somatic cell nuclear transfer without micromanipulators and carbon dioxide incubators using the Handmade Cloning (HMC) and the Submarine Incubation System (SIS)显示文摘 | Gábor Vajta Paul Bartels Jennifer Joubert Morné de la Rey Robert Treadwell Henrik Callesen | 2004 | Theriogenology2004，，8： | 1 |
| 8 | Effects of locally applied vascular endothelial growth factor and VEGF-inhibitor to the rabbit tibia during distraction osteogenesis显示文摘 | Henrik E Kristian G Knud S | 2003 | Journal of Orthopaedic Research2003，21，： | 1 |
| 9 | Water-oil partition profiling of Ionized drug molecules using cyclic voltammetry and a 96-well microfilter plate system显示文摘 | Sorina M Ulmeanu Henrik Jensen Gé raldine Bouchard | 2003 | Pharmaceutical Research2003，20，8： | 1 |
| 10 | Effect of a multifactorial intervention on mortality in type 2 diabetes显示文摘 | Peter G Henrik LA Hans-Henrik P | 2008 | N Engl J Med2008，358，6： | 1 |
| 11 | Model based scattering correction in time-of-flight cameras显示文摘 | S Henrik L Frank S G Christoph | 2014 | Opt Express2014，22，29： | 1 |
| 12 | Catalyst and process technologies for ultra low sulfur diesel显示文摘 | Kim G Knudsen Barry H Cooper Henrik Topsoe | | 0，，： | 1 |
| 13 | Barrier and surface properties of chitosan-coated greasepro of paper显示文摘 | Henrik K Mikael G Gunnar E | 2006 | Carbohydrate Polymers2006，65，： | 1 |
| 14 | A qualitative a- nalysis of burnout in elite Swedish athletes显示文摘 | Henrik G Peter H G6ran K Mattias J | 2008 | Psychology of Sport and Exercise2008，9，6： | 1 |
| 15 | Changes in the North Sea fish community: evidence of indirect effects of fishing 显示文摘 | Niels D Henrik G John G P | 2005 | ICES J Mar Sci2005，62，2： | 1 |
| 16 | Female aggression in European starling dining the breeding season 显示文摘 | Mafia I S Henrik G Smiht | 1997 | Anita behav1997，53，： | 1 |
| 17 | Effects of locally applied vascular endothelial growth factor (VEGF) and VEGF-inhibiter to the rabbit tibia during distraction ostecgenesis显示文摘 | Henrik Eckardt Kristian G Bundgaard Knud S Christensen | 2003 | J Orthop Res2003，21，2： | 1 |
| 18 | DDT化合物和PCB在富营养和贫营养湖中的季节性变化及其与藻类生物量之关系显示文摘1996~1997期间,在一个富营养湖(湖E)和一个贫营养湖(湖O)中进行了富营养化和有机污染物(PCB,DDTs及γ-HCH)的交互作用研究,两湖的地貌形态和水化学相似。集水区的土壤样品表明两湖暴露于相似的大气条件下。与湖O相比湖E没有观测到生物稀释。湖E的沉积物(1.5倍)、表面沉积物(1.4倍)和河鲈(Perca fluviatilis)(2.4倍)的有机碳和脂质物质中的PCB水平较高,并且微粒的沉降流较大,沉积物捕集器和沉淀物表面PCB的水平也较高。湖E中PCB的大部分转运主要是靠浮游植物。DDD/DDE比值较高似乎与p,p’-DDT的高负载相关而非厌氧的原因。所记录的湖O深层沉积岩心的高DDD/DDE比值和sDDT的高水平以及在此期间沉积最多,大概是由于从集水区流入的前体DDT最高的缘故。 | Maria Sderstrm Kerstin Nylund Ulf Jrnberg Gran Lithner Gran Rosén Henrik Kylin 邵平 樊恩源 | 2000 | AMBIO-人类环境杂志2000，29，4： | 1 |
| 19 | Detection of pulmonary embolism with combined ventilation-perfusion SPECT and low-dose CT: head-to-head comparison with multidetector CT angiography显示文摘 | Henrik G Jann M Claus VJ | 2009 | J Nucl Med2009，50，： | 1 |
| 20 | Good stability but high periprosthetic bone mineral loss and late-occurring periprosthetic fractures with use of uncemented tapered femoral stems in patients with a femoral neck fracture显示文摘 | Olof G Sk? ldenberg Helene Sj? ? Paula Kelly-Pettersson Henrik Bodé n Thomas Eisler André Stark Olle Muren | 2014 | Acta Orthopaedica2014，，4： | 1 |
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