PT  - JOURNAL ARTICLE
AU  - KIM, SANGMIN
AU  - HAN, JEONGHUN
AU  - KIM, JEE SOO
AU  - KIM, JUNG-HAN
AU  - CHOE, JUN-HO
AU  - YANG, JUNG-HYUN
AU  - NAM, SEOK JIN
AU  - LEE, JEONG EON
TI  - Silibinin Suppresses EGFR Ligand-induced CD44 Expression through Inhibition of EGFR Activity in Breast Cancer Cells
DP  - 2011 Nov 01
TA  - Anticancer Research
PG  - 3767--3773
VI  - 31
IP  - 11
4099  - http://ar.iiarjournals.org/content/31/11/3767.short
4100  - http://ar.iiarjournals.org/content/31/11/3767.full
SO  - Anticancer Res2011 Nov 01; 31
AB  - 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.