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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 | Diagnosis of goose circovirus infection in Hungarian geese samples using poly- merase chain reaction and dot blot hybridization tests 显示文摘 | Balla N W Smyth J A Weston J H | 2004 | Avian Pathol2004，33，1： | 1 |
| 4 | Structure-Stability Study of Cyclodextrin Complexes with Selected Vola- tile Hydrocarbon Contaminants of Soils显示文摘 | N Szaniszl6 E Fenyvesi J Balla | 2005 | Journal of Inclusion Phenomena and Macrocyclic Chemistry2005，53，34： | 1 |
| 5 | Microwave-sin- tered 3D printed tricalcium phosphate scaffolds for bone tis- sue engineering 显示文摘 | Tarafder S Balla V K Davies N M | 2013 | J Tissue Eng Regen M2013，7，8： | 1 |
| 6 | REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis 显示文摘 | Ballas N Grunseich C Lu DD | 2005 | Cell2005，121，4： | 1 |
| 7 | Stabilization oferythrocyte membranes by polyamies显示文摘 | BALLAS S K MOHANDAS N MARTON L J | 1983 | Proc Natl Acad Sci USA1983，80，7： | 1 |
| 8 | REST and its compressors mediate plasticity of neuronal gene chromatin throughout neuregenesis显示文摘 | Grunseich C Lu DD | 2005 | Cell2005，121，： | 1 |
| 9 | Transient expression of the plasmid pCaMVCAT in plant protoplasts following transformation with polyethyleneglycol显示文摘 | Ballas N Zakai N Loyter A | 1987 | Exp Cell Res1987，170，1： | 1 |
| 10 | Genotyping of Chlamydia trachomatis from the endocervical specimens of high-risk women in Hungary显示文摘 | Petrovay F Balla E Németh I | 2009 | J Med Microbiol2009，58，6： | 1 |
| 11 | Diagnosis of goose circovirus infection in Hungarian geese samples using polymerase chain reaction and dot blot hybridization tests 显示文摘 | Balla N W Smyth J A | 2004 | Avian Pathology2004，33，1： | 1 |
| 12 | Pelvic malakoplakia simulating recurrence of rectal adenocarcinoma: report of a case显示文摘 | Rafailidis SF Ballas KD Symeonidis N | 2009 | Tech Colopmctol2009，13，1： | 1 |
| 13 | Genomic organization and regulation of the human interleukin-18 gene显示文摘 | BALLAS K KOYAMA N | 2000 | Scand J Immunol2000，52，6： | 1 |
| 14 | Business at the Margins? Business Interests in Edge Urban Politics显示文摘 | Nick Phelps Parsons N Ballas D Dowling A | 2006 | International Journal of Urban and Regional Research2006，30，2： | 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 | Pathology of the optic nerve injury显示文摘 | Balla L Ianovici N Costin D | | 0，，4： | 1 |
| 17 | Genomic organization and regulation of the human interleukin-18 gene显示文摘 | KALINA U BALLAS K KOYAMA N | 2000 | Scand J Immunol2000，52，6： | 1 |
| 18 | Genomic organization and regulation of the human interleukin- 18 gene显示文摘 | Kalina U Ballas K Koyama N | 2000 | Scand J Imrnunol2000，52，6： | 1 |
| 19 | Pathology of the optic nerve injury显示文摘 | Balla L Ianovici N Costin D | 2012 | Rev Med Chir Soc Med Nat Iasi2012，116，4： | 1 |
| 20 | REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis显示文摘 | BALLAS N GRUNSEICH C LU D D | 2005 | Cell2005，121，4： | 1 |
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