DESCRIPTION (provided by applicant): The overall goal of this project is to discover novel, anti-inflammatory compounds from medicinal plants native to West Africa. The broad long-term objective is to establish a role for this unexploited source of natural products for future chemoprevention applications for colon and other cancers. The inflammatory process appears to be an important biological undercurrent in several common human cancers. Many inflammatory disease states increase the risk for cancer in a particular organ; gastritis for stomach cancer, and colitis for colon cancer are examples. Habitual use of non-steroidal anti-inflammatory drugs (NSAIDS) appears to reduce the risk for several types of human cancer, most notably, colon cancer. Yet, long-term use of NSAIDS in cancer chemoprevention is a complex issue, marred by major side effects including prolonged bleeding, ulceration, and risk of stroke; some of these events occur in even with the advent of selective COX-2 inhibitors. West Africa is rich in indigenous medicinal practices including knowledge and use of botanicals with wide anti-inflammatory effects. The hypothesis to be tested is that native medicinal plants from West Africa used traditionally for relief of pain, fever, and inflammation interacts to inhibit cyclooxgenases 1 and 2, implicated in corrupted cell signaling pathways co-opted by human tumors. We postulate that these African botanicals will have NSAID-like effects and will inhibit COX pathways involved in colon cancer, but will have the advantage of a wider margin of safety. The specific aims of this project are: 1) To develop chemical fingerprints of five West African plant extracts (neem tree, baobab tree, Senegal mahogany, African basil, and kinkirissi bush) as initial quality control measures and a starting panel for future fractionation and isolation of active principles 2). to determine if extracts (decoctions) of 5 West African medicinal plants have potential cytostatic or cytotoxic effects on a range of colon cancer cell lines differing in COX expression levels; 3) to determine whether extracts of African medicinal plants inhibit COX-1 and COX- 2 isoforms in colon cancer cell lines; and, 4) to determine if COX-dependent or independent pathways are involved in induction of apoptosis in colon cancer cell lines by the African botanicals selected for study. The methodologies used are RNA and protein expression assays for COX-1 and COX-2, standard dose response cytotoxicity assays using human colon cancer cell lines, and flow cytometry mediated detection of apoptosis and apoptotic proteins. The long-term goal of this project is to establish a biologically-driven fractionization program to further characterize active inhibitors detected in active African medicinal plants. We expect that having access to this unique source of bioactive natural products, combined with the use of both conventional and functional in vitro bioassays will lead to discovery of new chemopreventive agents which can be ultimately developed into clinically effective agents. We have unique access to actual plants with purported anti-inflammatory activity used by actual traditional healers in West Africa.
|Effective start/end date||2/3/06 → 1/31/10|
- National Institutes of Health: $153,723.00
- National Institutes of Health: $136,061.00