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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 | Observation of Coupled Magnetic and Electric Domains显示文摘 | Fiebig M Lottermoser Th Frhlich D | 2002 | Nature2002，419，： | 1 |
| 3 | Single mineral dating by the Pb-Pb step-leaching method: Assessing the mechanisms显示文摘 | Frei R Villa I M Nagler Th F Kramers J D | 1997 | Geochimica et Cosmochimica Acta1997，61，2： | 1 |
| 4 | Water flow and solute transport process in the unsaturated zone显示文摘 | Nielsen D R Van Genuchten M Th Biggar J W | 1986 | Water Resources Research1986，22，9： | 1 |
| 5 | Caloric equivalent of live weight loss of dairy cattle显示文摘 | Th Bath D L Ronning M Meyer J H | 1965 | J Dairy Sci1965，48，： | 1 |
| 6 | 查看详情显示文摘 | Landen O L Boehly T R Bradley D K Braun D G Callahan D A Celliers P M Collins G W Dewald E L Divol L Glenzer S H Hamza A Hicks D G Hoffman N Izumi N Jones O S Kirkwood R K Kyrala G A Michel P Milovich J Munro D H Nikroo A Olson R E Robey H F Spears B K Th | | 0，，： | 1 |
| 7 | Acid sphingomyelinase-ceramide system mediates effects of antidepressant drugs显示文摘 | Gulbins E Palmada M Reichel M Lüth A B?hmer C Amato D | 2013 | Nat Med2013，19，7： | 1 |
| 8 | Network awareness of P2P live streaming applications: a measurement study 显示文摘 | Ciullo D Garcia M A Horv A Th A | 2010 | IEEE Transac- tions on Multimedia2010，12，1： | 1 |
| 9 | Soil salinity mapping using spatio-temporal kriging and Bayesian maximum entropy with inter- val soft data显示文摘 | Douaik A Meirvenne M V To th D | 2005 | Geoderma2005，128，： | 1 |
| 10 | FMRI visualization of transient activations in the rat olfactory bulb using short odor stimulations显示文摘 | Martin C Grenier D Thévenet M etal | 2007 | Neuro Image2007，，36： | 1 |
| 11 | Proteinuria as amodiffiahle risk factor for progression of non-diabetic renal disease显示文摘 | Jafar TH Stark PC Schmid CH Landa M Mascantoni C de Zeeuw D | 2001 | Kidney Int2001，60，3： | 1 |
| 12 | Heavy metal accumulation and tolerance of energy grass ( Elymus elongatus subsp. ponticus cv. Szarvasi-1) grown in hydroponic culture显示文摘 | Gyula Sipos ádám Solti Viktória Czech Ildikó Vashegyi Brigitta Tóth Edit Cseh Ferenc Fodor | 2013 | Plant Physiology and Biochemistry2013，，： | 1 |
| 13 | Spatio-temporal Object-oriented Data Model for Disaggregate Travel Behavior显示文摘 | Frihida A Marceau D Th&iault M | 2002 | Transactions in GIS2002，6，3： | 1 |
| 14 | Should decompressive surgery be performed in malignant cerebral venous thrombosis?:a series of 12 patients显示文摘 | Théaudin M Crassard I Bresson D | | 0，，04： | 1 |
| 15 | Microcystin-LR induces abnormal root development by altering microtubule organization in tissue-cultured common reed (Phragmites australis) plantlets显示文摘 | Máthé C Beyer D | 2009 | Aquatic Toxicology2009，92，： | 1 |
| 16 | The farnesoid X receptor modulates adiposity and peripheral insulin sensitivity in mice显示文摘 | Cariou B van Harmelen K Duran-Sandoval D van Dijk TH Grefhorst A Abdelkarim M | | 0，，： | 1 |
| 17 | Observation of coupled magnetic and electric domains显示文摘 | FIEBIG M LOTTERMOSER Th FRHLICH D | 2002 | Na-ture2002，419，： | 1 |
| 18 | Characterization of the Saccharomyces cerevisiae high affinity copper transporter Ctr3 显示文摘 | PENA M M O PUIG S TH/ELE D J | 2000 | J Biol Chem2000，275，33： | 1 |
| 19 | Intrinsic and extrinsic point - defects in vapor transport grown ZnO bulk crystals 显示文摘 | Pfisterer D Hofmann D M Sann J Meyer B K Tena-Zaera R Munoz-Sanjose V Frank Th Pensl G | 2006 | Physica B2006，376，377： | 1 |
| 20 | Enhanced mechanical properties of laser treated Al-Cu alloy:a microstructural analvsis显示文摘 | De Mol van Otterloo J L Bagnoli D De Hosson J Th M | 1995 | Acta Metal Mater1995，43，7： | 1 |
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