Zerumbone suppresses EGF-induced CD44 expression through the inhibition of STAT3 in breast cancer cells.

Abstract

Expression of the CD44 gene is upregulated in breast cancer cells and is correlated with patient survival. Aberrant CD44 expression promotes tumor progression and metastasis. In the present study, we investigated the role of zerumbone (ZER) on regulatory mechanisms of CD44 expression in breast cancer cells. Our results showed that CD44 expression was significantly increased by epidermal growth factor receptor (EGFR) ligands in SKBR3 breast cancer cells. In contrast, EGF-induced CD44 expression was decreased by a MEK1/2 inhibitor, UO126, or STAT3 inhibitor, STAT3 VI, respectively. Notably, ZER downregulated the basal level of CD44 expression in CD44+ breast cancer cells. In addition, the induction of CD44 expression by EGFR ligands, EGF or TGF-α, was markedly decreased by ZER treatment. Finally, we investigated the inhibitory mechanism of ZER on EGF-induced CD44 expression. Our results showed that EGF-induced phosphorylation of STAT3 was completely suppressed by ZER. Collectively, ZER suppressed EGF-induced CD44 expression through inhibition of the STAT3 pathway. Therefore, we suggested that ZER may act as a promising therapeutic drug for the treatment of breast cancer.

• Authors: Sangmin Kim, Won Ho Kil, Jeongmin Lee, Soo-Jin Oh, Jeonghun Han, Myeongjin Jeon, Taewoo Jung, Se Kyung Lee, Soo Youn Bae, Hyun Chul Lee, Jun Ho Lee, Ha Woo Yi, Seok Won Kim, Seok Jin Nam, Jeong Eon Lee
• Journal: Oncology reports (Oncol Rep) Vol. 32 Issue 6 Pg. 2666-72 (Dec 2014) ISSN: 1791-2431 [Electronic] Greece
• PMID: 25269647 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD44 protein, human
• Hyaluronan Receptors
• STAT3 Transcription Factor
• Sesquiterpenes
• Transforming Growth Factor alpha
• zerumbone
• Epidermal Growth Factor
• ErbB Receptors

Topics

• Breast Neoplasms (drug therapy, genetics, pathology)
• Cell Line, Tumor
• Epidermal Growth Factor (genetics)
• ErbB Receptors
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Hyaluronan Receptors (biosynthesis)
• STAT3 Transcription Factor (antagonists & inhibitors, biosynthesis)
• Sesquiterpenes (administration & dosage)
• Signal Transduction (drug effects)
• Transcriptional Activation (drug effects)
• Transforming Growth Factor alpha (genetics)