Chemopreventive Agents of Plant Origin:Colon Ca

Efficacy of potential chemopreventive agents of plant origin in colon carcinogenesis.

Juliana K. Choi, Alison D. Pawlus, Bao-Ning Su, Dae Sik Jang, Genoveva Murillo, John M. Pezzuto, A. Douglas Kinghorn, Rajendra G. Mehta.

University of Illinois at Chicago, Chicago, IL.

Previous collaborative work in our laboratories has resulted in the isolation and identification of a large number of potential cancer chemopreventive agents obtained from edible and other plants via an activity-guided fractionation approach.

In this procedure, crude plant extracts exhibiting chemopreventive potential are chromatographically fractionated, and pure compounds responsible for the initial activity are structurally and biologically characterized.

For the present study, 34 such potential chemopreventive agents isolated in pure form from 11 plants were evaluated for their efficacy in a colon cancer in vitro model. Antiproliferative properties of these agents were determined in HT-29 human colon cancer cells over a seven-day period at a dose range of 0.1 ìM to 10 ìM.

Seven potential chemopreventive agents were selected which exhibited growth suppression greater than 70%. These comprised the rotenoids, á-toxicarol and sumatrol from Tephrosia toxicaria Pers. (Leguminosae; stems), the aminopyrrolidine diamide, odorine, from Aglaia ponapensis Kaneh. (Meliaceae), and the withanolides ixocarpalactone A, ixocarpalactone B, philadelphicalactone A, and withaphysacarpin from Physalis philadelphica Lam. (Solanaceae; leaves and stems).

Of these compounds, ixocarpalactone B and philadelphicalactone A are new compounds, and ixocarpalactone A and withphysacarpin are known constituents of the fruits of P. philadelphica, which are known as tomatillos and are commonly used in salsas in Mexican cuisine.

Three of these agents inhibited cell proliferation with an IC50 of less than 1 ìM, reaching to nearly 100% inhibition at 10 ìM concentration.

These results were confirmed with the SW480 and SW620 human colon cell lines.

Moreover, a study has been initiated to determine the effects of ixocarpalactone A on azoxymethane-induced aberrant crypt foci in CF-1 mice.

AACR Abstract Number: 4786, 2003

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