Anticancer activities and the drug targets of botanical saponins from a medicinal herb, gynostemma pentaphyllum

Abstract

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 4985 Triterpenoid saponins are complex molecules produced by most plant species through complex biosynthetic pathways. These plant metabolites play important roles to humans owing to their diverse medicinal effects, including antiinflammatory, antimicrobial, and anticancer activities. In our laboratory, we have been investigating the anticancer activities of a mixture of triterpenoid saponins (designated GpMix) extracted from a medicinal plant, Gynostemma pentaphyllum known as Jiaogulan or southern ginseng in China. We found that the GpMix effectively inhibits the growth of tumor cells. Intriguingly, the inhibitory effects of GpMix require the presence of co-cultivated normal cells. The GpMix is also able to substantially reduce the number of polyps in the Min/+ mice that are predisposed to colon cancer. The potential gene targets of GpMix were investigated. Based on the results obtained from western, northern blotting analysis and protein expression in situ, GpMix does not affect the transforming ability, subcellular localization, or the level of Ras protein. Instead, the Raf-1 protein was found to be totally degraded within 2 days of GpMix treatment. In addition, alteration of phosphorylation of the Erk1/2 genes was detected upon GpMix treatment. Further proteomic analyses revealed that a wide spectrum of glycolytic and energy metabolic gene products were downregulated in cells treated with GpMix. Literatures showed that majority of tumor cells overexpress glycolytic enzymes to compensate the low rate of ATP synthesis. Our findings may provide a conceptually novel approach by which the growth of cancer cells can be suppressed through the reduction of the cellular glycolytic activities.