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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 | Induction of heme oxygenase is a ralpid,protective reslponse in rhabdomyolysis in the rat显示文摘 | Balla G | 1992 | J Clin Invest1992，90，1： | 1 |
| 3 | Induction of hemecxygenase is a rapid, protective response in rhabdomyolysis in the rat 显示文摘 | Nath KA Balla G Veroellotfi GM | 1992 | J Clin Invest1992，90，： | 1 |
| 4 | Response of wheat fungal diseases to elevated atmospheric COz leve显示文摘 | Beneze S Vida G Balla K | 2013 | Cereal Reseatx''h Communications2013，，41： | 1 |
| 5 | Design of drug-resistant alleles of type-IIIphosphatidylinositol 4-kinases using mutagenesis and molecular modeling显示文摘 | Balla A Tuymetova G Toth B | 2008 | Biochemistry2008，47，6： | 1 |
| 6 | Red blood cell,hemoglobin and heme in the progression of atherusclerosis 显示文摘 | Jeney V Balla G Balla J | 2014 | Front Physio12014，5，： | 1 |
| 7 | Ferritin:a cytoprotective antioxidant stratagem of endothelium 显示文摘 | Balla G Jacob HS Balla J Rosenberg M Nath K Apple F | 1992 | J Biol Chem1992，257，18： | 1 |
| 8 | Delineation of a CpG phosphorothioate oligodeoxynucleotide for activating primate immune responses in vitro and in vivo显示文摘 | Hartmann G Weeratna RD Ballas ZK | 2000 | J Immunol2000，164，3： | 1 |
| 9 | Heine,heme oxy-genase and ferritin in vascular endothelial cell injury显示文摘 | BALLA J VERCELLOTTI G M JENEY V | 2005 | Mol Nutr Food Res2005，49，： | 1 |
| 10 | Ferritin: a cytoprotective antioxidant strategem of endothelium显示文摘 | BALLA G JACOB H S BALLA J | 1992 | J Biol Chem1992，267，18： | 1 |
| 11 | Hemin: a possible physiological mediator of low density lipoprotein oxidation and endothelial injury显示文摘 | BALLA G JACOB H S EATON J W | 1991 | Arterioscler Thromb1991，11，6： | 1 |
| 12 | Association of left ventricular hypertrophy with metabolic risk factors: the Hy- perGEN study显示文摘 | DE SIMONE G PALMIED V BALLA JN | 2002 | Hypertens2002，20，2： | 1 |
| 13 | Safety of bowel resection for colorectal surgical emergency in the elderly显示文摘 | Pavlidis TE Marakis G Ballas K | 2006 | Colorectal Dis2006，8，8： | 1 |
| 14 | Delineation of a CpG phosphorothioate oligodeoxynucleotide for activating primate immune responses in vitro and in vivo显示文摘 | Hartmann G Weeratna RD Ballas ZK | 2000 | J Immunol2000，164，： | 1 |
| 15 | Sertoli cell proliferation in the fetal and neonatal rattestis:a continuous phenomenon显示文摘 | ANGELOPOULOU R BALLA M LAVRANOS G etal | 2008 | Acta Histochem2008，110，4： | 1 |
| 16 | Delineation of a CpG phosphorothioate oligodeoxynucleotide for activating primate immunein responses vitro and in vivo显示文摘 | Hartmann G Weeratna RD Ballas ZK | 2000 | Immunol2000，164，3： | 1 |
| 17 | Delineation of a CpG phosphorothioate oligodeoxynucleotide for activating primate immune responses in vitro and in vivo显示文摘 | Hartmann G Weeratna RD Ballas ZK | 2000 | J Immunol2000，164，3： | 1 |
| 18 | Alpha - methylacyl - CoA racemase (AMACR/P504S) can distinguish hepatocellular carcinoma and dysplastic hepatocytes from benign nondysplastic hepatocytes 显示文摘 | GUZMAN G WU S J KAJDACSY - BALLA A | 2006 | Appl Immunohistochem Mol Morphol2006，14，4： | 1 |
| 19 | Safety of bowel resection for colorectal surgical emergency in the elderly显示文摘 | Pavlidis TE Marakis G Ballas K | 2006 | Colorectal Dis2006，8，8： | 1 |
| 20 | Delineation of a CpG phophorothioate oligideoxynucleotides for Activity primate Immune Response In Vitor and In Vivo 显示文摘 | Hartmann G Weerantna RD Ballas ZK | 2000 | J Immmunol2000，164，3： | 1 |
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