Anti-proliferative effects of calcitriol on endothelial cells derived from two different microenvironments
Calcitriol (1,25-dihydroxycholecalciferol), the active form of Vitamin D, is anti-proliferative in tumor cells and tumor-derived endothelial cells (TDEC). However, endothelial cells isolated from normal tissues as cell lines or freshly isolated cells or from implanted Matrigel plugs (MDEC) are relat...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
2007
|
| Subjects: | |
| Online Access: | http://eprints.um.edu.my/5034/1/Chung-2007-Anti-proliferative_e.pdf |
| _version_ | 1825719029082357760 |
|---|---|
| author | Chung, I. Yu, W.D. Karpf, A.R. Flynn, G. Bernardi, R.J. Modzelewski, R.A. Johnson, C.S. Trump, D.L. |
| author_facet | Chung, I. Yu, W.D. Karpf, A.R. Flynn, G. Bernardi, R.J. Modzelewski, R.A. Johnson, C.S. Trump, D.L. |
| author_sort | Chung, I. |
| collection | UM |
| description | Calcitriol (1,25-dihydroxycholecalciferol), the active form of Vitamin D, is anti-proliferative in tumor cells and tumor-derived endothelial cells (TDEC). However, endothelial cells isolated from normal tissues as cell lines or freshly isolated cells or from implanted Matrigel plugs (MDEC) are relatively resistant. Both TDEC and. MDEC express similar amounts of Vitamin D receptor (VDR) protein. Although the VDR from TDEC has higher binding affinity for calcitriol than those from MDEC, VDR in both cell types translocates to the nucleus and transactivates the 24-hydroxylase promoter-luciferase construct. Calcitriol selectively inhibits the growth of TDEC but not MDEC by inducing G(0)/G(1) cell cycle arrest and by promoting apoptosis. This selectivity appears to be related to 24-hydroxylase (CYP24) expression. Calcitriol significantly induced CYP24 expression in MDEC but not in TDEC and inhibition of CYP24 activity in MDEC restores their sensitivity to calcitriol. These findings indicate that the induction of CYP24 expression differs in endothelial cells isolated from different microenvironments (TDEC versus MDEC) and that this distinction contributes to selective calcitriol-mediated growth inhibition in these cell types. (c) 2006 Elsevier Ltd. All rights reserved. |
| first_indexed | 2024-03-06T05:13:24Z |
| format | Article |
| id | um.eprints-5034 |
| institution | Universiti Malaya |
| language | English |
| last_indexed | 2024-03-06T05:13:24Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | um.eprints-50342013-03-14T02:19:24Z http://eprints.um.edu.my/5034/ Anti-proliferative effects of calcitriol on endothelial cells derived from two different microenvironments Chung, I. Yu, W.D. Karpf, A.R. Flynn, G. Bernardi, R.J. Modzelewski, R.A. Johnson, C.S. Trump, D.L. R Medicine Calcitriol (1,25-dihydroxycholecalciferol), the active form of Vitamin D, is anti-proliferative in tumor cells and tumor-derived endothelial cells (TDEC). However, endothelial cells isolated from normal tissues as cell lines or freshly isolated cells or from implanted Matrigel plugs (MDEC) are relatively resistant. Both TDEC and. MDEC express similar amounts of Vitamin D receptor (VDR) protein. Although the VDR from TDEC has higher binding affinity for calcitriol than those from MDEC, VDR in both cell types translocates to the nucleus and transactivates the 24-hydroxylase promoter-luciferase construct. Calcitriol selectively inhibits the growth of TDEC but not MDEC by inducing G(0)/G(1) cell cycle arrest and by promoting apoptosis. This selectivity appears to be related to 24-hydroxylase (CYP24) expression. Calcitriol significantly induced CYP24 expression in MDEC but not in TDEC and inhibition of CYP24 activity in MDEC restores their sensitivity to calcitriol. These findings indicate that the induction of CYP24 expression differs in endothelial cells isolated from different microenvironments (TDEC versus MDEC) and that this distinction contributes to selective calcitriol-mediated growth inhibition in these cell types. (c) 2006 Elsevier Ltd. All rights reserved. 2007 Article PeerReviewed application/pdf en http://eprints.um.edu.my/5034/1/Chung-2007-Anti-proliferative_e.pdf Chung, I. and Yu, W.D. and Karpf, A.R. and Flynn, G. and Bernardi, R.J. and Modzelewski, R.A. and Johnson, C.S. and Trump, D.L. (2007) Anti-proliferative effects of calcitriol on endothelial cells derived from two different microenvironments. Journal of Steroid Biochemistry and Molecular Biology, 103 (3-5). pp. 768-770. ISSN 0960-0760, |
| spellingShingle | R Medicine Chung, I. Yu, W.D. Karpf, A.R. Flynn, G. Bernardi, R.J. Modzelewski, R.A. Johnson, C.S. Trump, D.L. Anti-proliferative effects of calcitriol on endothelial cells derived from two different microenvironments |
| title | Anti-proliferative effects of calcitriol on endothelial cells derived from two different microenvironments |
| title_full | Anti-proliferative effects of calcitriol on endothelial cells derived from two different microenvironments |
| title_fullStr | Anti-proliferative effects of calcitriol on endothelial cells derived from two different microenvironments |
| title_full_unstemmed | Anti-proliferative effects of calcitriol on endothelial cells derived from two different microenvironments |
| title_short | Anti-proliferative effects of calcitriol on endothelial cells derived from two different microenvironments |
| title_sort | anti proliferative effects of calcitriol on endothelial cells derived from two different microenvironments |
| topic | R Medicine |
| url | http://eprints.um.edu.my/5034/1/Chung-2007-Anti-proliferative_e.pdf |
| work_keys_str_mv | AT chungi antiproliferativeeffectsofcalcitriolonendothelialcellsderivedfromtwodifferentmicroenvironments AT yuwd antiproliferativeeffectsofcalcitriolonendothelialcellsderivedfromtwodifferentmicroenvironments AT karpfar antiproliferativeeffectsofcalcitriolonendothelialcellsderivedfromtwodifferentmicroenvironments AT flynng antiproliferativeeffectsofcalcitriolonendothelialcellsderivedfromtwodifferentmicroenvironments AT bernardirj antiproliferativeeffectsofcalcitriolonendothelialcellsderivedfromtwodifferentmicroenvironments AT modzelewskira antiproliferativeeffectsofcalcitriolonendothelialcellsderivedfromtwodifferentmicroenvironments AT johnsoncs antiproliferativeeffectsofcalcitriolonendothelialcellsderivedfromtwodifferentmicroenvironments AT trumpdl antiproliferativeeffectsofcalcitriolonendothelialcellsderivedfromtwodifferentmicroenvironments |