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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 | P300 in mild cognitive impairment and in dementia 显示文摘 | Egerh6zi A Glaub T Balla P | 2008 | Psychiatr Hung2008，23，5： | 1 |
| 3 | Molecular basis of asymptomatic β-thalassaemia major in an African American individual显示文摘 | Cai S P Gabuzda T | 1997 | Am J Med Genet1997，69，2： | 1 |
| 4 | Rapidly inducible changes in phosphatidylinositol 4, 5 -bisphosphate levels influ ence multiple regulatory functions of the lipid in intact living cells显示文摘 | Varnai P Thyagarajan B Rohacs T Balla T | 2006 | J Cell Biol2006，175，： | 1 |
| 5 | Towards elucidation of the lignin degradation pathway in actinomycetes显示文摘 | Godden B BallA S Helvenstein P | 1992 | J Gen Microbiol1992，138，： | 1 |
| 6 | Ziprasldone: a novel psyehotropic with unique properties 显示文摘 | Goodniek J Ballas P | 2004 | Expert Rev Nexerother2004，14，： | 1 |
| 7 | Competitive canalization of PIN-dependent auxin flow from axillary buds controls pea bud outgrowth显示文摘 | Balla J Kalousek P Reinohl V Friml J Procházka S | 2011 | Plant Journal2011，65，4： | 1 |
| 8 | Cardiac resynchronization therapy increases plasma levels of the endogenous inotrope apelin显示文摘 | Salvati A Balla C | 2007 | Eur J Heart Fail2007，9，3： | 1 |
| 9 | STIM and Orai: the long-awaited constituents of store-operated calcium entry显示文摘 | Varnai P Hunyady L and Balla T | 2009 | Trends Pharmacol Sci2009，30，3： | 1 |
| 10 | Goodness-of-fit indexes in confirmatory factor analysis: The effect of sample size显示文摘 | Marsh H W BALLA J R MCDONALD R P | 1988 | Psychological Bulletin1988，103，： | 1 |
| 11 | Goodness-of-fit indexes in confirmatory factor analysis:The effect of sample size显示文摘 | Marsh H W Balla J R McDonald R P | 1988 | Psychological Bulletin1988，103，3： | 1 |
| 12 | Dual regulation of TRPV1 by phosphoinositides显示文摘 | Lukacs V Thyagarajan B Varnai P Balla A Balla T Rohacs T | 2007 | J Neurosci2007，27，： | 1 |
| 13 | P300 in mild cognitive im- pairment and in dementia 显示文摘 | Eqerhazi A Glaub T Balla P | 2008 | Psychiatr Hung2008，23，3： | 1 |
| 14 | Inflammation and resistance to erythropoiesis-stimulating agents-what do we know and what needs to be clarified显示文摘 | Smrzova J Balla J Barany P | | 0，，8： | 1 |
| 15 | Effect of gypsum on proliferation and differentiation of MC3T3-E1 mouse osteoblastic cells显示文摘 | áron Lazáry Bernadett Balla János P. Kósa Krisztián Bácsi Zsolt Nagy István Takács Péter P. Varga Gábor Speer Péter Lakatos | 2006 | Biomaterials2006，，3： | 1 |
| 16 | P300 in mild cognitive impairment and in dementia显示文摘 | Egerházi A Glaub T Balla P | 2008 | Psychiatr Hung2008，23，5： | 1 |
| 17 | Automated neuropsychological test battery in depression - preliminary data显示文摘 | Egerhazi A Balla P Ritzl A | 2013 | Neuropsy cho- pharmalogia Hungarica2013，15，1： | 1 |
| 18 | The Penicillium chrysogenum-derived antifungal poptide shows no toxic effects on mammalian cells in the intended therapeutic concentration显示文摘 | Sappanos H Szigeti G P Pal B Rnsznak Z Szucs G Rajnovolgyi E Balla J Balla G Nagy E Leitor E Pocsi I Marx F Csernoch L | 2005 | Nannyn Schmiedeberg''s Arch Pharmacol2005，371，： | 1 |
| 19 | Serum paraoxonase activity changes in patients with Alzheimer's disease and vascular dementia显示文摘 | Paragh G Balla P Degrell I | 2002 | Eur Arch Psychiatry Clin Neurosci2002，252，2： | 1 |
| 20 | P300 in mild cogni- tive impairment and in dementia显示文摘 | Egerhazi A Glaub T Balla P | 2008 | Psychiatr Hung2008，23，5： | 1 |
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