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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 | Towards a unified paradigm for sequence‐based identification of fungi显示文摘 | Urmas K?ljalg R. Henrik Nilsson Kessy Abarenkov Leho Tedersoo Andy F. S. Taylor Mohammad Bahram Scott T. Bates Thomas D. Bruns Johan Bengtsson‐Palme Tony M. Callaghan Brian Douglas Tiia Drenkhan Ursula Eberhardt Margarita Due?as Tine Grebenc Gareth W. Gri | 2013 | Mol Ecol2013，，21： | 2 |
| 3 | Effects of Intense Low-Density Lipoprotein Cholesterol Reduction in Patients With Stroke or Transient Ischemic Attack: The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Trial显示文摘 | Pierre Amarenco Larry B. Goldstein Michael Szarek Henrik Sillesen Amy E. Rudolph Alfred Callahan Michael Hennerici Lisa Simunovic Justin A. Zivin K Michael A. Welch | 2007 | Stroke2007，，： | 2 |
| 4 | Friction generated limit cycles显示文摘 | Olsson Henrik Astrom K J | 2001 | IEEE Transactions on Control Systems Technology2001，9，4： | 1 |
| 5 | An Experimental and Numerical Crashworthiness Investigation of Thermoplastic Composite Crash Boxes显示文摘 | Hamidreza Z Matthias K Henrik A | 2008 | Composite Structure2008，85，3： | 1 |
| 6 | Antioxidant activity of Cod ( Gadus morhua ) protein hydrolysates: Part 1 – In vitro assays and evaluation in 5% fish oil-in-water emulsion显示文摘 | K.H. Sabeena Farvin Lisa Lystb?k Andersen Henrik Hauch Nielsen Charlotte Jacobsen Greta Jakobsen Inez Johansson Flemming Jessen | 2013 | Food Chemistry2013，，： | 1 |
| 7 | Are CO2 taxes regressive? Evindence from danish experience 显示文摘 | Wier M Birr-Petersen K Henrik K J | 2005 | Ecological Economics2005，52，： | 1 |
| 8 | Accuracy of migration analysis in hip arthroplasty Digitized and conventional radiography, compared to radiostereometry in 51 patients显示文摘 | Henrik Malchau Johan K? rrholm Yu Xing Wang Peter Herberts | 1995 | Acta Orthopaedica1995，，5： | 1 |
| 9 | Intracerebral infusion of glial cell line-derived neurotrophic factor promotes striatal neurogenesis after stroke in adult rats显示文摘 | TOHRU K HENRIK A PAR T et ol | 2006 | Stroke2006，37，9： | 1 |
| 10 | High symbiont re- latedness stabilizes mutualistic cooperation in fungus-growing termites显示文摘 | Aanen D K Henrik H Debets A J M | 2009 | Science2009，326，5956： | 1 |
| 11 | Di(2-ethylhexyl) adipate (DEHA) induced developmental toxicity but not antiandrogenic effects in pre- and postnatally exposed Wistar rats显示文摘 | Majken Dalgaard Ulla Hass Anne Marie Vinggaard Kirsten Jarfelt Henrik R Lam Ilona K S?rensen Helle M Sommer Ole Ladefoged | 2003 | Reproductive Toxicology2003，，2： | 1 |
| 12 | Micromotion of femoral stems in total hip arthroplasty显示文摘 | Johan K Henrik M Gothenberg | 1994 | J Bone Joint Surg1994，，： | 1 |
| 13 | Specific bacterial, archaeal, and eukaryotic communities in tidal-flat sediments along a vertical profile of several meters显示文摘 | Reinhard W Henrik S Beate K | 2006 | Applied and Environmental Microbiology2006，72，4： | 1 |
| 14 | Electrocoagulation as a Remediation Tool for Wastewaterscontaining Arsenicv显示文摘 | Henrik K Hansen Patricio Nuez Rodrigo Grandon | 2006 | Minerals Engineering2006，19，： | 1 |
| 15 | The UNITE database for molecular identification of fun-gi-recent updates and future perspectives显示文摘 | Abarenkov K Henrik Nilsson R Larsson K H | 2010 | The NewPhytologist2010，186，： | 1 |
| 16 | Micromotion of femoral stem m total hip arthroplasty: A randomized study of cemented,hydroxapatite-coated and porous-coated stems with roentgen sterophotogrammetri analysis显示文摘 | Johan K Henrik M Finnur S Peter H | 1994 | Joura of Bone Joint Surg1994，76，11： | 1 |
| 17 | A System for Information Management in Simulation of Manufacturing Processes 显示文摘 | HENRIK JOHANSSON PETER ASTROM K JELL ORSBORN | 2009 | Advances in Engineering Software2009，35，11： | 1 |
| 18 | Simulation of wear characteristics of engine cylinders显示文摘 | Jorgen Bottiger Henrik K Reitz | 2002 | Wear2002，253，： | 1 |
| 19 | Fast-track hip and knee replacement- what are the issues显示文摘 | Henrik K Kjeld S | 2010 | Acta Orthop2010，81，3： | 1 |
| 20 | Measles in Europe: an epidemiological assessment显示文摘 | Mark Muscat Henrik Bang Jan Wohlfahrt Steffen Glismann K?re M?lbak | 2009 | The Lancet2009，，9661： | 1 |
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