A55

Objective

Plants produce chemical compounds to prevent encroachment by competitors. These turf wars that generate defense products in plants have potential medicinal value for humans. For example, compounds with anti-angiogenic properties are useful in combating cancer by preventing new blood vessel formation to support the tumor. The search for new angiogenesis inhibitors is ongoing, and utilizes a variety of time-intensive cell culture models. In this report we introduce a rapid, inexpensive method for screening potential anti-angiogenic compounds in a model system that stimulates the production of secondary defense chemicals in plants, thus increasing the potential yield of effective compounds.

Plant chemicals under investigation for anti-angiogenic activity include flavonoids, a broad group of compounds that are present in most photosynthesizing cells of plants. Flavonoids share a common phenyl-chromanone structure (C6-C3-C6), and include thousands of compounds, subdivided into 6 major categories; flavones, flavonols, isoflavones, flavanols, flavanones, and anthocyanins. Humans do not synthesize flavonoids, but derive an average of 1 gram per day in their diet. Their reported pharmacological properties include antioxidative, anti-inflammatory and antiproliferative properties.

Methods

In order to induce defense chemical production, we chose thyme and mint plants to combine because thyme was observed to inhibit the spread of mint, a highly invasive vascular plant. The thyme plants grown alone, as well as the mint alone, were analyzed as controls. The plant leaves and stems were extracted and the flavonoid products were analyzed by reverse phase HPLC. The flavonoids that appear in the thyme in the presence of mint, that are not present in the thyme plants grown alone, were considered induced by the presence of mint. The induced compounds were collected and tested in a vertical plate assay that measures root length as a quantitative assay for drug sensitivity. The compounds were applied to the vascular root tissue of mint seedlings 5-7 days after germination.

Results

Of eight Thymus vulgaris compounds that were induced by the presence of mint, 5 were tested by bioassay, and one was found to have an inhibitory effect. Known angiogenesis inhibitors, VEGF receptor tyrosine kinase and amelioride hydrochloride, significantly reduced root growth compared to the control. An HPLC-isolated compound b, which eluted at 15.2 minutes, reduced the growth of root vascular tissue compared to the control and vehicle control, and 50% as well as known angiogenesis inhibitors.

Conclusion

This report demonstrates that induced secondary defense chemicals produced by thyme plants include flavonoid compounds. Useful inhibitors may be identified with this rapid, sensitive, and inexpensive technique.

Citation Information: Cancer Prev Res 2008;1(7 Suppl):A55.

Seventh AACR International Conference on Frontiers in Cancer Prevention Research-- Nov 16-19, 2008; Washington, DC