American ginseng (Panax Quinquefolius L.) extract alters mitogen-activated protein kinase cell signaling and inhibits proliferation of MCF-7 cells

Ginseng has been shown to inhibit cancer cell proliferation and tumor growth, however the mechanisms underlying this inhibition have yet to be elucidated. An inhibitory effect of hot water-extracted American ginseng (Panax quinquefolius L.) root on cell proliferation was demonstrated using MCF-7 human breast cancer cells treated with a wide concentration range of the ginseng extract (GE) for 6 days. The effects of GE were concentration-dependent with an IC50 of 0.49 mu g/mu l and the minimum exposure time to elicit an inhibitory response was 24 hours. Using an antibody microarray, it was determined that several key cell survival proteins were altered in GE-treated cells, including several members of the mitogen-activated protein kinase (MAPK) family. A GE-induced decrease in phospho-MEK1/2 and -ERK1/2 and an increase in phospho-Raf-1 were observed and verified using Western blot analysis. Furthermore, mRNA and protein expression of the Raf-1 kinase inhibitor protein (RKIP) was shown to be transiently, yet significantly, upregulated following GE treatment. These results suggest that American ginseng may act to inhibit breast cancer cell proliferation by increasing the expression of RKIP, resulting in inhibition of the MAPK pathway. This novel mechanism has implications in the potential prevention and treatment of breast cancer.