The main goal of this research is to discover new natural products from blue-green algae (cyanobacteria) and marine animals possessing algal symbionts that will be useful as drugs in the treatment of cancer or its prevention and/or as pharmacological tools for the study of chemical carcinogenesis. Ne isolates of blue-green algae will be grown in culture for anticancer evaluation. Research to-date has concentrated mainly on the rapid-growing, relatively abundant cyanophytes found predominantly in terrestrial ecosystems and belonging to the order Nostocales. The proposed research will focus on the slower-growing and rarer blue-green algae, particularly those found in marine environments. Sponges, tunicates, and other marine invertebrates that harbor cyanophytes and prochlorophytes will also be collected for anticancer evaluation. Extracts of the cultured cyanophytes and the marine animals containing algal symbionts will be prepared and tested for cytotoxicity using the KB cell line (a human epidermoid carcinoma of the nasopharynx). The extracts will also be evaluated for tumor-promoting and anti-tumor-promoting activity using the Epstein-Barr virus-induced transformation by 12-0-tetradecanoylphorbol-13-acetate in Raji cells assay. Using these bioassays to monitor fractionation of the active principles in the most promising leads, the cytotoxic, tumor-promoting, and anti-tumor-promoting compounds will be isolated and their molecular structures, including absolute stereochemistries, will be elucidated by a combination of chemical and physical methods. The cytotoxic agents will be evaluated further for selective cytotoxicity in the National Cancer Institute's human cancer cell line panel. For example, the potent cytotoxins in the cultured cyanophytes Scytonema burmanicum (UH isolate D)-4-1) and Plectonema fortii (UH isolate DO-321-2), the algal- containing sponge Sarcotragus sp. for Guam, and that algal-containing didemnid tunicate SG-37 from Guam will be isolated, identified, and evaluated as anticancer agents.
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