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- Title
Mitogen-activated protein kinase (MAPK) pathway mediates the oestrogen-like activities of ginsenoside Rg1 in human breast cancer (MCF-7) cells.
- Authors
Wai-Sum Lau; Wen-Fang Chen; Robbie Yat-Kan Chan; De-An Guo; Man-Sau Wong; Lau, Wai-Sum; Chen, Wen-Fang; Chan, Robbie Yat-Kan; Guo, De-An; Wong, Man-Sau
- Abstract
<bold>Background and Purpose: </bold>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.<bold>Experimental Approach: </bold>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 (ERalpha), as well as ERalpha 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.<bold>Key Results: </bold>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.<bold>Conclusions and Implications: </bold>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 ERalpha via MEK/ERK in a ligand-independent manner.
- Subjects
MITOGEN-activated protein kinases; ESTROGEN; BREAST cancer; CANCER cells; STEROID hormones; PROTEIN metabolism; PROTEINS; BIOCHEMISTRY; RESEARCH; FLAVONOIDS; RESEARCH methodology; GLYCOSIDES; CELL physiology; EVALUATION research; MEDICAL cooperation; CELLULAR signal transduction; PHENOMENOLOGY; COMPARATIVE studies; TRANSFERASES; GENISTEIN; PROTEIN-tyrosine kinases; CELL lines; PHOSPHORYLATION; BREAST tumors; CHEMICAL inhibitors
- Publication
British Journal of Pharmacology, 2009, Vol 156, Issue 7, p1136
- ISSN
0007-1188
- Publication type
journal article
- DOI
10.1111/j.1476-5381.2009.00123.x