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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 | Electron paramagnetic resonance studies of rndical species of proanthocyanidins and gallate esters 显示文摘 | Bors W Michel C Stettmaier K | 2000 | Arch Biochem Biophys2000，374，2： | 1 |
| 3 | Antioxidant capacity of flavanols and gallate esters: pulse radiolysis studies显示文摘 | Bors W Michel C | 1999 | Free Radic Bio Med1999，27，1112： | 1 |
| 4 | Flavonoid antioxidant: Rate constants for reaction with oxygen radicals显示文摘 | Bors W Michel C Saram M | 1994 | Methods Enzymol1994，234，： | 1 |
| 5 | Projection distortion analysis for flattened image mosaicing from straight uniform generalized cylinders显示文摘 | Puech W Bors AG Pitas I | 2001 | Pattern Recognition2001，34，： | 1 |
| 6 | Nutritional enhance- ment of biocontrol of blue mold on apples 显示文摘 | JANISIEWICZ W J USALL J BORS B | 1992 | Phytopatholo- gy1992，82，： | 1 |
| 7 | Antioxidant Properties of Roasted Coffee Residues显示文摘 | WEN J Y BOR S W LEE W C | 2005 | Journal of Agricuhural and Food Chemistry2005，53，： | 1 |
| 8 | Chemistry of the antioxidant effect of polyphenols显示文摘 | Bors W Michel C | 2002 | Ann NY Acad Sci2002，957，： | 1 |
| 9 | Antioxidant capacity of flavanols and gallate esters: pulse radiolysis studies 显示文摘 | Bors W Michel C | 1999 | Free Radic Biol Med1999，27，1112： | 1 |
| 10 | Effect of marchantins and related compounds on 5-lipoxygenase and cyclooxygenase and their antioxidant properties: a structure - activity relationship study 显示文摘 | Schwartner C Bors W Michel C | 1995 | Phytomedicine1995，2，2： | 1 |
| 11 | Antioxidant capacity of flavanols and gallate esters: pulse radiolysis Studies显示文摘 | Bors W Michel C | 1999 | Free radical biology medicine1999，27，： | 1 |
| 12 | Innate immunity in Arabidopsis thaliana:Lipopolysaccharides activate nitric oxide synthase (NOS) and induce defense genes显示文摘 | Zeidler D Zahringer U Gerber I Dubery I Hartung T Bors W Hutzler P Durner J | | 0，，： | 1 |
| 13 | Long-term outcomes of infant behavioral dysregulation显示文摘 | Hyde R O'Callaghan MJ Bor W | 2012 | Pediatrics2012，130，5： | 1 |
| 14 | Studies on radical intermediatesin the early stage of the nonenzymatic browning reaction of carbohydratesand amino acids显示文摘 | HOFMANN T BORS W STETTMAIER K | 1999 | Journal of Agricultural&Food Chemistry1999，47，2： | 1 |
| 15 | Maternal anxiety and depression, poverty and marital relationship factors during early child- hood as predictors of anxiety and depressive symptoms in adolescence 显示文摘 | SPENCE SH NAJMAN JM BOR W | 2002 | J Child Psychol Psych2002，43，4： | 1 |
| 16 | Control of storage decay of apples with Sporobolomyces roseus显示文摘 | Peterson D L Bors R | 1994 | Plant Disease1994，78，： | 1 |
| 17 | Kinetic study offlavonoid reactions with stable radicals显示文摘 | Butkovi6 V Klasinc L Bors W | 2004 | Journal of Agricultural and Food Chemistry2004，52，10： | 1 |
| 18 | Dynamic changes of matrix metalloproteinases and their tissue inhibitors in severe sepsis显示文摘 | Diána M Bálint N Gábor W | 2011 | J Crit Care2011，26，6： | 1 |
| 19 | Radical scavenging by flavonoid antioxidants显示文摘 | Bors W Saran M | 1987 | Free Radical Res Commun1987，，2： | 1 |
| 20 | Development of asphalt pavement fatigue cracking prediction model based on loading mode transfer function显示文摘 | Jiang M Y Bor W T Xiao Z | 2012 | Road Materials and Pavement Design2012，13，3： | 1 |
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