IOVS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

(Investigative Ophthalmology and Visual Science. 2003;44:4192-4199.)
© 2003 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.02-1198
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Audo, I.
Right arrow Articles by Nickells, R. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Audo, I.
Right arrow Articles by Nickells, R. W.

Vitamin D Analogues Increase p53, p21, and Apoptosis in a Xenograft Model of Human Retinoblastoma

Isabelle Audo,1 Soesiawati R. Darjatmoko,1 Cassandra L. Schlamp,1 Janice M. Lokken,1 Mary J. Lindstrom,2 Daniel M. Albert,1 and Robert W. Nickells1,3

1From the Departments of Ophthalmology and Visual Sciences, 2Biostatistics, and 3Physiology, University of Wisconsin-Madison Medical School, Madison, Wisconsin.

PURPOSE. To study the antineoplastic effect of vitamin D analogues in a xenograft model of human retinoblastoma.

METHODS. Athymic mice were injected subcutaneously with Y79 cells and treated 5 days a week with either mineral oil (control group) or the vitamin D analogues calcitriol or 1,25-dihydroxy-16-ene-23-yne vitamin D3 (16,23-D3). BrdU was injected 1 hour before death. Animals were killed after 1, 2, 3, or 5 weeks. Paraffin-embedded sections of the tumors were studied for cell proliferation by monitoring for BrdU incorporation and cell death by terminal transferase dUTP-nick end labeling (TUNEL), 3'-overhang ligation, and histology. Sections of the tumors were immunostained for p53 and p21.

RESULTS. There was no significant difference in incorporation of BrdU among the three groups, suggesting that cell proliferation is unaffected by vitamin D analogues. TUNEL was increased in tumors treated with vitamin D analogues compared with the control group. This increase was statistically significant for calcitriol in the time frame examined, but not statistically significant for 16,23-D3. Alternatively, the ratio of proliferation to cell death was significantly different for both calcitriol and 16,23-D3 compared with control tumors after 3 weeks of treatment. Dying cells contained DNA strand breaks with overhanging nucleotides and nuclear changes characteristic of apoptosis. There was an increase in staining for p53 and p21 in areas associated with cell death in specimens treated with vitamin D analogues.

CONCLUSIONS. Vitamin D analogues appear to attenuate retinoblastoma tumor growth in athymic mice by increasing apoptosis. Cell death is associated with the upregulation of both p53 and p21.




This article has been cited by other articles:


Home page
 Cancer Prevention ResearchHome page
H. J. Lee, S. Paul, N. Atalla, P. E. Thomas, X. Lin, I. Yang, B. Buckley, G. Lu, X. Zheng, Y.-R. Lou, et al.
Gemini Vitamin D Analogues Inhibit Estrogen Receptor-Positive and Estrogen Receptor-Negative Mammary Tumorigenesis without Hypercalcemic Toxicity
Cancer Prevention Research, November 1, 2008; 1(6): 476 - 484.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
D. M. Albert, E. A. Scheef, S. Wang, F. Mehraein, S. R. Darjatmoko, C. M. Sorenson, and N. Sheibani
Calcitriol Is a Potent Inhibitor of Retinal Neovascularization
Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 2327 - 2334.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Verlinden, G. Eelen, I. Beullens, M. Van Camp, P. Van Hummelen, K. Engelen, R. Van Hellemont, K. Marchal, B. De Moor, F. Foijer, et al.
Characterization of the Condensin Component Cnap1 and Protein Kinase Melk as Novel E2F Target Genes Down-regulated by 1,25-Dihydroxyvitamin D3
J. Biol. Chem., November 11, 2005; 280(45): 37319 - 37330.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. J. Taverna, J.-L. Selam, and G. Slama
Association between a Protein Polymorphism in the Start Codon of the Vitamin D Receptor Gene and Severe Diabetic Retinopathy in C-Peptide-Negative Type 1 Diabetes
J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4803 - 4808.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
X. Zhang, F. Jiang, P. Li, C. Li, Q. Ma, S. V. Nicosia, and W. Bai
Growth Suppression of Ovarian Cancer Xenografts in Nude Mice by Vitamin D Analogue EB1089
Clin. Cancer Res., January 1, 2005; 11(1): 323 - 328.
[Abstract] [Full Text] [PDF]

Home page
 Arch OphthalmolHome page
D. M. Albert, A. Kumar, S. A. Strugnell, S. R. Darjatmoko, J. M. Lokken, M. J. Lindstrom, and S. Patel
Effectiveness of Vitamin D Analogues in Treating Large Tumors and During Prolonged Use in Murine Retinoblastoma Models
Arch Ophthalmol, September 1, 2004; 122(9): 1357 - 1362.
[Abstract] [Full Text] [PDF]

Home page
 Arch OphthalmolHome page
D. M. Albert, A. Kumar, S. A. Strugnell, S. R. Darjatmoko, J. M. Lokken, M. J. Lindstrom, C. M. Damico, and S. Patel
Effectiveness of 1{alpha}-Hydroxyvitamin D2 in Inhibiting Tumor Growth in a Murine Transgenic Pigmented Ocular Tumor Model
Arch Ophthalmol, September 1, 2004; 122(9): 1365 - 1369.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z. Zhang, H. Wang, M. Li, S. Agrawal, X. Chen, and R. Zhang
MDM2 Is a Negative Regulator of p21WAF1/CIP1, Independent of p53
J. Biol. Chem., April 16, 2004; 279(16): 16000 - 16006.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2003 by the Association for Research in Vision and Ophthalmology