| AJTR Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Am J Transl Res 1(1):80-86;2009
Original Article
Silibinin suppresses CD44 expression in prostate cancer cells
Alina M. Handorean, Kui Yang, Eric W. Robbins, Thomas Flaig, Kenneth A. Iczkowski
Department of Pathology, University of Colorado Health Science Center, Aurora, Colorado; Department of
Urologic Oncology, University of Colorado Health Science Center, Aurora, Colorado.
Received December 20, 2008; accepted December 30, 2008; available online January 1, 2009
Abstract: Prostate cancer (PCa), like most human cancers, features dysregulated CD44 expression. Expression
of CD44 standard (CD44s), present in benign epithelium, is lost in PCa while pro-invasive splice variant isoform
CD44v7-10 is overexpressed. The role of CD44 in silibinin’s anti-growth effects was uncertain. To assess
silibinin’s effects on CD44 promoter activity, PC-3M PCa cells were transfected with luciferase-CD44 promoter
construct 24 h prior to 25-200 µM silibinin treatment for 48 h. Also, cells’ expression of CD44 RNA (by qRT-PCR)
and protein (Western blot analysis) was studied. Silibinin was further tested preoperatively on a pilot cohort of 6
men with PCa compared with 7 matched placebo-treated men, with immunostaining for CD44v7-10 in their
prostates. In PC-3M cells, silibinin dose-dependently inhibited CD44 promoter activity up to 87%, caused a 90%
inhibition of total CD44 and 70% decrease in CD44v7-10 RNA, and at the protein level, decreased total CD44 at
100-200 µM dose and decreased CD44v7-10 after 3 days. Silibinin decreased adhesion to hyaluronan and
fibronectin. Silibinin at 100-200 µM inhibited Egr-1, a regulator of CD44 promoter activity. Thus, CD44 inhibition
is one mechanism by which silibinin reduces PCa tumorigenicity. (AJTR812002).
Key Words: Silibinin, prostatic neoplasms; CD44; plasmid; alternate splicing; adhesion
Full Text PDF
Address all correspondence to:
Kenneth A. Iczkowski, MD
Pathology—P.O. Box 6511
UCHSC—Campus Mail Stop 8104
Aurora, CO 80010
Tel: 303-724-0155
Fax: 303-724-3712
E-mail: Kenneth.Iczkowski@UCDenver.edu
Original Article
Silibinin suppresses CD44 expression in prostate cancer cells
Alina M. Handorean, Kui Yang, Eric W. Robbins, Thomas Flaig, Kenneth A. Iczkowski
Department of Pathology, University of Colorado Health Science Center, Aurora, Colorado; Department of
Urologic Oncology, University of Colorado Health Science Center, Aurora, Colorado.
Received December 20, 2008; accepted December 30, 2008; available online January 1, 2009
Abstract: Prostate cancer (PCa), like most human cancers, features dysregulated CD44 expression. Expression
of CD44 standard (CD44s), present in benign epithelium, is lost in PCa while pro-invasive splice variant isoform
CD44v7-10 is overexpressed. The role of CD44 in silibinin’s anti-growth effects was uncertain. To assess
silibinin’s effects on CD44 promoter activity, PC-3M PCa cells were transfected with luciferase-CD44 promoter
construct 24 h prior to 25-200 µM silibinin treatment for 48 h. Also, cells’ expression of CD44 RNA (by qRT-PCR)
and protein (Western blot analysis) was studied. Silibinin was further tested preoperatively on a pilot cohort of 6
men with PCa compared with 7 matched placebo-treated men, with immunostaining for CD44v7-10 in their
prostates. In PC-3M cells, silibinin dose-dependently inhibited CD44 promoter activity up to 87%, caused a 90%
inhibition of total CD44 and 70% decrease in CD44v7-10 RNA, and at the protein level, decreased total CD44 at
100-200 µM dose and decreased CD44v7-10 after 3 days. Silibinin decreased adhesion to hyaluronan and
fibronectin. Silibinin at 100-200 µM inhibited Egr-1, a regulator of CD44 promoter activity. Thus, CD44 inhibition
is one mechanism by which silibinin reduces PCa tumorigenicity. (AJTR812002).
Key Words: Silibinin, prostatic neoplasms; CD44; plasmid; alternate splicing; adhesion
Full Text PDF
Address all correspondence to:
Kenneth A. Iczkowski, MD
Pathology—P.O. Box 6511
UCHSC—Campus Mail Stop 8104
Aurora, CO 80010
Tel: 303-724-0155
Fax: 303-724-3712
E-mail: Kenneth.Iczkowski@UCDenver.edu
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