Berberine Inhibits Proliferation and Down-Regulates Epidermal Growth Factor Receptor through Activation of Cbl in Colon Tumor Cells

CORC > 厦门大学 > 生命科学－已发表论文

	Berberine Inhibits Proliferation and Down-Regulates Epidermal Growth Factor Receptor through Activation of Cbl in Colon Tumor Cells
	Wang, Lihong ; Cao, Hailong ; Lu, Ning ; Liu, Liping ; Wang, Bangmao ; Hu, Tianhui ; Israel, Dawn A. ; Peek, Richard M., Jr. ; Polk, D. Brent ; Yan, Fang ; Hu TH(胡天惠)
刊名	http://dx.doi.org/10.1371/journal.pone.0056666
	2013
关键词	CANCER-CELLS COLORECTAL-CANCER GENOTOXIC STRESS EGF RECEPTOR APOPTOSIS PATHWAYS MECHANISM ADENOMAS ARREST DEATH
英文摘要	National Institutes of Health [R01DK081134, R01DK56008]; National Nature Science Foundation of China [81070283, 30971524, 81172284]; NIH grant [P30DK058404]; Berberine, an isoquinoline alkaloid, is an active component of Ranunculaceae and Papaveraceae plant families. Berberine has been found to suppress growth of several tumor cell lines in vitro through the cell-type-dependent mechanism. Expression and activation of epidermal growth factor receptor (EGFR) is increased in colonic precancerous lesions and tumours, thus EGFR is considered a tumour promoter. The aim of this study was to investigate the effects and mechanisms of berberine on regulation of EGFR activity and proliferation in colonic tumor cell lines and in vivo. We reported that berberine significantly inhibited basal level and EGF-stimulated EGFR activation and proliferation in the immorto Min mouse colonic epithelial (IMCE) cells carrying the APC(min) mutation and human colonic carcinoma cell line, HT-29 cells. Berberine acted to inhibit proliferation through inducing G1/S and G2/M cell cycle arrest, which correlated with regulation of the checkpoint protein expression. In this study, we also showed that berberine stimulated ubiquitin ligase Cbl activation and Cbl's interaction with EGFR, and EGFR ubiquitinylation and down-regulation in these two cell lines in the presence or absence of EGF treatment. Knock-down Cbl expression blocked the effects of berberine on down-regulation of EGFR and inhibition of proliferation. Furthermore, berberine suppressed tumor growth in the HT-29 cell xenograft model. Cell proliferation and EGFR expression level was decreased by berberine treatment in this xenograft model and in colon epithelial cells of APC(min/+) mice. Taken together, these data indicate that berberine enhances Cbl activity, resulting in downregulation of EGFR expression and inhibition of proliferation in colon tumor cells.
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/90609]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Wang, Lihong,Cao, Hailong,Lu, Ning,et al. Berberine Inhibits Proliferation and Down-Regulates Epidermal Growth Factor Receptor through Activation of Cbl in Colon Tumor Cells[J]. http://dx.doi.org/10.1371/journal.pone.0056666,2013.
APA	Wang, Lihong.,Cao, Hailong.,Lu, Ning.,Liu, Liping.,Wang, Bangmao.,...&胡天惠.(2013).Berberine Inhibits Proliferation and Down-Regulates Epidermal Growth Factor Receptor through Activation of Cbl in Colon Tumor Cells.http://dx.doi.org/10.1371/journal.pone.0056666.
MLA	Wang, Lihong,et al."Berberine Inhibits Proliferation and Down-Regulates Epidermal Growth Factor Receptor through Activation of Cbl in Colon Tumor Cells".http://dx.doi.org/10.1371/journal.pone.0056666 (2013).