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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 | Data processing of digital recording of microscopic examination of urinary sediment显示文摘 | Lakatos J Bodor T Zidarics Z | 2000 | Clin Chem Acta2000，297，122： | 1 |
| 3 | Characterization of the co-caine-and amphetamine-regulated transcript(CART)peptide gene promot-er and its activation by a cyclic AMP-dependent signaling pathway in GH3cells显示文摘 | DOMINGUEZ G LAKATOS A KUHAR M J | 2002 | J Neurochem2002，80，5： | 1 |
| 4 | Effect of alkaline materials on interfacial rheological properties of oil-water wystems 显示文摘 | 1 Lakatos | 1999 | Colloid Polym Sci1999，277，： | 1 |
| 5 | Coals as sorbents for the removal and reduction of hexavalent chromium from aqueous waste streams显示文摘 | LAKATOS J BROWN S D SNAPE C E | 2002 | Fuel2002，81，5： | 1 |
| 6 | Data processing of digital recording of microscopic examination of urinary sediment显示文摘 | Lakatos J Bodor T Zidarics Z | 2000 | Clinica Chimica Acta2000，297，12： | 1 |
| 7 | Once-yearly zoledronic acid for treatment of post-menopausal osteoporosis显示文摘 | Black DM Delmas PD Eastell R Reid IR Boonen S Cauley JA Cosman F Lakatos P Leung PC Man Z Mautalen C Mesenbrink P Hu H Caminis J Tong K Rosario-Jansen T Krasnow J Hue TF Sellmeyer D Eriksen EF Cummings SR HORIZON Pivotal Fracture Trial | | 0，，： | 1 |
| 8 | Olfactory ensheathing cells and schwann cells differ in their in vitro interactions with astrocytes显示文摘 | Lakatos A Franklin R J Barnett SC | 2000 | Glia2000，32，3： | 1 |
| 9 | Low temperature in-hibits RNA silencing -mediated defence by the control of siRNAgeneration显示文摘 | SZITTYA G SILHAVY D MOLNAR A HAVELDA Z LOVAS A LAKATOS L BANFALVI Z B'URGYAN J | 2003 | EMBO J2003，22，： | 1 |
| 10 | Data processing of digital recordings of microscopic examination of urinary sediment 显示文摘 | LAKATOS J BODOR T ZIDARICS Z | 2000 | Clinica Chimica Acta2000，297，： | 1 |
| 11 | Early prophylactic bone grafting of high-energy tibial fractures显示文摘 | Blick SS Brumback R J Lakatos R | 1989 | Clin Orthop Relat Res1989，240，： | 1 |
| 12 | Data processing of digital recording of microscopic examination of urinary sediment显示文摘 | Bodor T Zidaries Z | 2000 | Clin Chem Acta2000，297，12： | 1 |
| 13 | Data processing of digital recordings of microscopic examination of urinary sediment显示文摘 | Lakatos J Bodor T Zidarics Z | 2000 | Clin Chim Acta2000，297，12： | 1 |
| 14 | Total hip arthroplasty with ace- tabular reconstruction using a bulk autograft for patients with de- velopmental dysplasia of the hip results in high loosening rates at mid-term follow-up显示文摘 | Zahar A Papik K Lakatos J | 2014 | Int Ortbop2014，38，5： | 1 |
| 15 | Serial long-term assessment of the natural history of asymptomatic patients with chronic aortic regurgitation and normal left ventricular systolic function显示文摘 | Bonow R O Lakatos E Maron B J | 1991 | Circulation1991，84，4： | 1 |
| 16 | Data processing of digital recording of microscopic examination of urinary sediment显示文摘 | Lakatos J Bodor T Zidarics Z | 2000 | Clin Chem Acta2000，297，12： | 1 |
| 17 | Angiogenic effects of LMWH in patients with stable coronary disease, A pilot study 显示文摘 | Quyyumi A A Diodati J G Lakatos E | 1993 | J Am Coll Cardiol1993，22，： | 1 |
| 18 | Early prophylactic bone grafting of high-energy tibial fractures 显示文摘 | Blick S S Brumback R J Lakatos R | 1989 | Clin Orthop Relat Res1989，，240： | 1 |
| 19 | Increasing local levels of neuregulin (glial growth factor-2) by direct infusion into areas of demyelination does not alter remyelination in the rat CNS显示文摘 | Penderis J Woodruff RH Lakatos A | 2003 | Eur J Neurosci2003，18，8： | 1 |
| 20 | The prevalence and incidence of Helicobacter pylori infections among young recruits during service in the Hungarian Army显示文摘 | Furesz J Lakatos S Nemeth K | 2004 | Helicobacter2004，9，1： | 1 |
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