A Novel Natural Inhibitor of Extracellular Signal-Regulated Kinases and Human Breast Cancer Cell Growth
Ernest B. Izevbigie*1, Joseph L. Bryant and Alice Walker* *
The Molecular Genetics and Molecular & Cellular Signaling Laboratory, Department of Biology, and National Institutes of Health Center for Environmental Health, Jackson State University, Jackson, Mississippi 39217; and Institute of Human Virology, Animal Model Division, University of Maryland Biotechnology Institute, Baltimore, Maryland 21201
Water-soluble extracts of edible Vernonia amygdalina leaves were recently reported as potent inhibitors of cultured MCF-7cells. The mechanism by which V. amygdalina inhibits MCF-7 cell growth has not been previously studied. The objective of this study was to evaluate the effects of V. amygdalina on the activities,DNA synthesis, and subsequent cell growth of extracellular signal-regulated protein kinases 1 and 2 (ERKs 1/2;). Treatment of cells with various concentrations (3–100 mg/ml) of water-solubleV. amygdalina extract potently inhibited ERK activities, DNA synthesis (P < 0.005), and cell growth (P < 0.01) in a concentration-dependent fashion, both in the absence and presence of serum. The growth rate of cells pretreated with 10 mg/mlV. amygdalina for 48 hrs before transfer to V. amygdalina-free medium was not significantly different (P > 0.05) from untreated cells. These results suggest that V. amygdalina, at least at concentrations up to 10 mg/ml, exhibits cytostatic action to retard the growth of human breast cancer cells. In addition,the ERK signaling pathways may be one or more of the intracellular targets for V. amygdalina antineoplastic actions.
Discovery of Water-Soluble Anticancer Agents (Edotides) from a Vegetable Found in Benin City, Nigeria
Ernest B. Izevbigie
Molecular Genetics and Molecular and Cellular Signaling Laboratory, Department of Biology, and Center for Environmental Health, Jackson State University, Jackson, Mississippi 39217
Abstract Cancer claims the lives of more than six million people each year in the world. About 1,268,000 new cancer cases, and 553,400deaths were reported in the United States in 2001. Current treatment approaches have yielded significant progress in the fight against cancer, but the incidence of developing certain types of cancer continues to rise. This is especially true in the African-American communities. African Americans are about 33% more likely todie of cancer than are whites and more than twice likely to die of cancer as are Asian-Islander, American-Indians, and Hispanics.This increase coupled with the harsh side effects of some of the cancer chemotherapies have led to the search for more natural biological products, especially those derived from plant products,currently known as herbal medicine. There is a need for a continuedsearch for novel natural products that may be used as cancer chemopreventive and/or chemotherapeutic agents. The objectiveof this study was to evaluate the effect(s) of a novel water-solubleleaf extract of Vernonia amygdalina (VA) on human breast cancer cell DNA synthesis. MCF-7 cell line, considered a suitable model,was used in this study. Treatment of cells with physiologically relevant concentrations of water-soluble VA extract potently inhibited DNA synthesis in a concentration-dependent fashion both in the absence and presence of serum. Fractions of VA extract separated using preparative reverse-phase chromatography also inhibited DNA synthesis (P < 0.005). These results suggest that VA vegetable, if incorporated in the diet, may prevent or delay the on-set of breast cancer.