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Research ArticleExperimental Studies

Silibinin Suppresses EGFR Ligand-induced CD44 Expression through Inhibition of EGFR Activity in Breast Cancer Cells

SANGMIN KIM, JEONGHUN HAN, JEE SOO KIM, JUNG-HAN KIM, JUN-HO CHOE, JUNG-HYUN YANG, SEOK JIN NAM and JEONG EON LEE
Anticancer Research November 2011, 31 (11) 3767-3773;
SANGMIN KIM
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JEONGHUN HAN
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JEE SOO KIM
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JUNG-HAN KIM
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JUN-HO CHOE
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JUNG-HYUN YANG
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SEOK JIN NAM
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  • For correspondence: sjnam@skku.edu paojlus@hanmail.net
JEONG EON LEE
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  • For correspondence: sjnam@skku.edu paojlus@hanmail.net
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Abstract

CD44, the transmembrane receptor for hyaluronan, is implicated in tumor cell invasion and metastasis. The expression of CD44 and its variants is associated with poor prognosis in breast cancer. Here, we investigated the effect of silibinin (a polyphenolic flavonolignan of the herbal plant of Silybum marianum, milk thistle) on the epidermal growth factor (EGF) ligand-induced CD44 expression in human breast cancer cells. The levels of CD44 mRNA and protein expression were greatly increased by EGF and by TGF-α in SKBR3 and BT474 breast cancer cells. In contrast, EGFR ligand-induced CD44 expression was reduced by EGFR inhibitors, AG1478 and lapatinib, respectively. Interestingly, we observed that EGFR ligand-induced CD44 and matrix metalloproteinase-9 (MMP-9) expression was reduced by silibinin treatment in a dose-dependent manner. In addition, silibinin suppressed the EGF-induced phosphorylation of EGFR and extracellular signal-regulated kinase1/2 (ERK1/2), a downstream signaling molecule of EGFR. Therefore, we suggest that silibinin prevents the EGFR signaling pathway and may be used as an effective drug for the inhibition of metastasis of human breast cancer.

  • Silibinin
  • CD44
  • EGFR
  • EGF
  • TGF-α
  • MMP-9
  • breast cancer metastasis
  • Received August 8, 2011.
  • Revision received September 22, 2011.
  • Accepted September 27, 2011.
  • Copyright© 2011 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 31 (11)
Anticancer Research
Vol. 31, Issue 11
November 2011
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Silibinin Suppresses EGFR Ligand-induced CD44 Expression through Inhibition of EGFR Activity in Breast Cancer Cells
SANGMIN KIM, JEONGHUN HAN, JEE SOO KIM, JUNG-HAN KIM, JUN-HO CHOE, JUNG-HYUN YANG, SEOK JIN NAM, JEONG EON LEE
Anticancer Research Nov 2011, 31 (11) 3767-3773;

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Silibinin Suppresses EGFR Ligand-induced CD44 Expression through Inhibition of EGFR Activity in Breast Cancer Cells
SANGMIN KIM, JEONGHUN HAN, JEE SOO KIM, JUNG-HAN KIM, JUN-HO CHOE, JUNG-HYUN YANG, SEOK JIN NAM, JEONG EON LEE
Anticancer Research Nov 2011, 31 (11) 3767-3773;
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