Native American medicinal plants are traditionally used to prevent and treat a variety of diseases, including cancer. These herbal preparations are alleged to have many biological activities, such as stimulation or suppression of immune responses and antiproliferative effects on cancer cells. In the present study, we investigated the effects of aqueous and ethanol extracts from two Native American plants, Ligusticum porteri (Osha) and Anemopsis californica (Yerba Manza), on the growth of human MCF-7/AZ breast and HCT8/E11 colon cancer cells. The aqueous and ethanol extracts from A. californica potently inhibited growth of MCF-7/AZ in a concentration-dependent manner, whereas the growth of HCT8/E11 was unaltered. Extracts from L. porteri showed no activity on either cell line. In addition, we observed that the extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) activities were markedly decreased when exposed to both extracts from A. californica. These results suggest that the growth inhibitory effect of A. californica in breast cancer cells is ERK-mediated.