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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 | Stabilization of erythrocyte membranes by polyamines显示文摘 | Mohandas N Marton L J | 1983 | Pro Nat Acad Sci1983，80，： | 1 |
| 3 | Postoperative adhesion prevention using a statin-containing cellulose film in an experimental model显示文摘 | Lalountas M Ballas K D Michalakis A | | 0，，： | 1 |
| 4 | 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 |
| 5 | Fabrication of compositionally and structurally graded Ti-TiO2 structures using laser engineered net shaping ( LENS ) 显示文摘 | Vamsi Krishna B Balla V K | 2009 | Acta Biomaterialia2009，5，： | 1 |
| 6 | 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 |
| 7 | Is more ever too much:the number of indicators per factor in confirmatory factor analysis显示文摘 | Marsh H W Han K T Balla J R Grayson | 1998 | Multivariate Behavioral Research1998，33，2： | 1 |
| 8 | 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 |
| 9 | Once-monthly subcutaneous CERA maintains stable hemoglobin control in patients with chronic kidney disease on dialysis and converted directly from epoetin one to three times weekly 显示文摘 | Sulowicz W Locatelli F Ryckelynck JP Balla J Csiky B Harris K | 2007 | Clin J Am Soc Nephrol2007，2，4： | 1 |
| 10 | Additive manufac- turing of Co-Cr-Mo alloy: influence of heat treatment on mi- erostructure, tribological, and electrochemical properties 显示文摘 | Mantrala M K Das M Balla V K | 2015 | Frontiers in Mechanical Engineering2015，，1： | 1 |
| 11 | Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA显示文摘 | Ballas Z K Rasmussen W L Krieg A M | 1996 | J Immunol1996，157，5： | 1 |
| 12 | Carbon monoxide generated by heme oxygenase-1 suppresses the rejection of mouse-to-rat cardiac transplants显示文摘 | Sato K Balla J Otterbein L | 2001 | J Immunol2001，166，6： | 1 |
| 13 | Carbon monoxide generated by heme oxygenase-1 suppresses the rejection of mouse-to-rat cardiac transplants显示文摘 | Sato K Balla J Otterbein L | 2001 | J Immunol2001，166，： | 1 |
| 14 | Risk factors influenc- ing conversion of laparoscopic to open eholecystectomy 显示文摘 | Pavlidis TE Marakis GN Ballas K | 2007 | J Laparoendosc Adv Surg Tech A2007，17，4： | 1 |
| 15 | Processing of Bulk Alumina Ceramics Using Laser Engineered Net Shaping显示文摘 | Balla V K Bose S Bandyopadhyay A | | 0，，03： | 1 |
| 16 | Natural killer cells in human health and diseases显示文摘 | Orange J S Ballas Z K | 2006 | Clin Immunol2006，118，： | 1 |
| 17 | The decreased activity of lactase phlorizin hydrolase and bone mineral density in postmenopausal women显示文摘 | Bacsi K Kosa JP Balla B | 2007 | J Bone Mine Res2007，22，1： | 1 |
| 18 | Carbon monoxide generated by heme oxygenase-1 suppresses the rejection of mouse-to- rat cardiac transplants显示文摘 | Sato K Balla J Otterbein L | 2001 | J Immunol2001，166，6： | 1 |
| 19 | Carbon monoxide generated by heme oxygenase- 1 suppresses the rejection of mouse- to- rat cardiac transplants显示文摘 | Sato K Balla J Otterbein L | 2001 | J Immunol2001，166，6： | 1 |
| 20 | 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 |
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