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[Cancer Research 59, 2644-2649, June 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 2644-2649, June 1, 1999]
© 1999 American Association for Cancer Research

Experimental Therapeutics

1,25-Dihydroxycholecalciferol (1,25-D3) Inhibits the Growth of Squamous Cell Carcinoma and Down-Modulates p21Waf1/Cip1 in Vitro and in Vivo1

Pamela A. Hershberger2, Ruth A. Modzelewski, Zoya R. Shurin, Robert M. Rueger, Donald L. Trump and Candace S. Johnson

Departments of Pharmacology [P. A. H., R. A. M., Z. R. S., R. M. R., C. S. J.] and Medicine [D. L. T., C. S. J.] and The University of Pittsburgh Cancer Institute [D. L. T., C. S. J.], University of Pittsburgh, Pittsburgh, Pennsylvania 15213

1,25-Dihydroxycholecalciferol (1,25-D3) has significant antitumor effects in the murine squamous cell carcinoma (SCC) tumor model in vitro and in vivo. We investigated the basis for this antiproliferative activity and found that, in vitro, 1,25-D3 administration is associated with altered expression of cell cycle regulatory proteins, treatment results in retinoblastoma dephosphorylation, decreased expression of p21Waf1/Cip1 (p21) mRNA and protein, and increased expression of p27Kip1 (p27) mRNA and protein. Dexamethasone, which acts synergistically with 1,25-D3 to inhibit SCC proliferation, enhanced 1,25-D3-induced down-modulation of p21 without affecting the ability of 1,25-D3 to increase p27 expression. 1,25-D3 did not induce cleavage of poly(ADP-ribose) polymerase. These in vitro data suggest that 1,25-D3 exerts antitumor activity in SCC by perturbing cell cycle progression rather than by inducing apoptosis. In vivo, a 1,25-D3 treatment regimen that results in a decrease in SCC tumor volume is associated with a statistically significant decrease in intratumoral p21 expression. p21 expression is not changed in tumors isolated from control animals or animals treated with a nontherapeutic dose of 1,25-D3. Intratumoral p27 levels were not modulated by 1,25-D3 treatment. Thus, both in vitro and in vivo, 1,25-D3-mediated growth inhibition is associated with p21 down-modulation.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1999 by the American Association for Cancer Research.