Mitogen-activated protein kinase (MAPK) pathway mediates the oestrogen-like activities of ginsenoside Rg1 in human breast cancer (MCF-7) cells

doi:10.1111/j.1476-5381.2009.00123.x

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	Mitogen-activated protein kinase (MAPK) pathway mediates the oestrogen-like activities of ginsenoside Rg1 in human breast cancer (MCF-7) cells
	Lau, Wai-Sum 2,4; Chen, Wen-Fang 3,4; Chan, Robbie Yat-Kan 2,4; Guo, De-An1 ; Wong, Man-Sau 2,4
刊名	BRITISH JOURNAL OF PHARMACOLOGY
	2009-04
卷号	156 期号:7 页码:1136-1146
关键词	MAPK ER alpha phytoestrogens ginsenoside Rg1
ISSN号	0007-1188
DOI	10.1111/j.1476-5381.2009.00123.x
文献子类	Article
英文摘要	The present study was designed to determine how ginsenoside Rg1, an active ingredient in ginseng root, exerts its oestrogenic effects. We hypothesize that Rg1 may exert oestrogen-like actions in MCF-7 cells by activating the mitogen-activated protein kinase (MAPK) pathway in a ligand-independent manner. MCF-7 cells were co-incubated with the MAPK inhibitor PD98059 to determine whether the stimulant effects of Rg1 on cell proliferation, the induction of IGF-IR and pS2, the functional transactivation of oestrogen receptor-alpha (ER alpha), as well as ER alpha phosphorylation are dependent on MAPK. The time-dependent responses of mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated protein kinase (ERK) to Rg1 in MCF-7 cells were studied. The responses of MEK phosphorylation to Rg1 in oestrogen receptor (ER)-negative HEK293 cells were also determined. The effects of Rg1 on cell proliferation and IGF-IR protein expression were studied in the presence of tyrosine kinase inhibitor genistein to elucidate the involvement of tyrosine kinase in mediating these effects. The oestrogenic effects of Rg1 in MCF-7 cells were abolished in the presence of PD98059. Rg1 could induce MEK protein expression and the phosphorylation level of MEK and ERK significantly in a time- and dose-dependent manner. Rg1 activated MEK phosphorylation in ER-negative HEK293 cells in a time- and dose-dependent manner. Rg1 induction of cell proliferation and IGF-IR protein expression was abolished by co-treatment with genistein. Taken together, these results show that the MAPK pathway is involved in mediating the oestrogen-like actions of Rg1 in MCF-7 cells and suggest that Rg1 may activate ER alpha via MEK/ERK in a ligand-independent manner.
资助项目	Hong Kong Special Administrative Region, China[AOE/P-10/01] ; RGC General Research Fund[5636/07M] ; The Hong Kong Polytechnic University[00000000]
WOS关键词	FACTOR-I RECEPTOR ; LIGAND-INDEPENDENT ACTIVATION ; GROWTH-FACTOR RECEPTOR ; DIETARY PHYTOESTROGENS ; GENISTEIN ; ALPHA ; PHOSPHORYLATION ; MECHANISMS
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	WILEY-BLACKWELL
WOS记录号	WOS:000264783300012
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279270]
专题	上海中药现代化研究中心
通讯作者	Wong, Man-Sau
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, Shanghai Res Ctr TCM Modernizat, Shanghai 200031, Peoples R China 2.State Key Lab Chinese Med & Mol Pharmacol, Shenzhen, Peoples R China; 3.Qingdao Univ, Coll Med, Dept Physiol, Qingdao 266071, Peoples R China; 4.Hong Kong Polytech Univ, Dept Appl Biol & Chem Technol, Inst Mol Technol Drug Discovery & Synth, Cent Lab, Kowloon, Hong Kong, Peoples R China;
推荐引用方式 GB/T 7714	Lau, Wai-Sum,Chen, Wen-Fang,Chan, Robbie Yat-Kan,et al. Mitogen-activated protein kinase (MAPK) pathway mediates the oestrogen-like activities of ginsenoside Rg1 in human breast cancer (MCF-7) cells[J]. BRITISH JOURNAL OF PHARMACOLOGY,2009,156(7):1136-1146.
APA	Lau, Wai-Sum,Chen, Wen-Fang,Chan, Robbie Yat-Kan,Guo, De-An,&Wong, Man-Sau.(2009).Mitogen-activated protein kinase (MAPK) pathway mediates the oestrogen-like activities of ginsenoside Rg1 in human breast cancer (MCF-7) cells.BRITISH JOURNAL OF PHARMACOLOGY,156(7),1136-1146.
MLA	Lau, Wai-Sum,et al."Mitogen-activated protein kinase (MAPK) pathway mediates the oestrogen-like activities of ginsenoside Rg1 in human breast cancer (MCF-7) cells".BRITISH JOURNAL OF PHARMACOLOGY 156.7(2009):1136-1146.