The main goal of this research is to isolate, identify, and evaluate new anticancer compounds from field-collected and cultured blue-green algae (cyanobacteria). Extracts of blue-green algae will be screened for cytotoxicity against human epidermoid carcinoma of the nasopharynx cells (KB) and a mouse fibroblast cell line (NIH3T3) and for antineoplastic activity in vivo against murine P-388 lymphocytic leukemia and murine Lewis lung carcinoma. Using one of more of these bioassays to monitor the fractionation of active extracts, cytotoxic and/or antitumor compounds will be isolated from the algae and their molecular structures, including absolute stereo-chemistries, will be elucidated by a combination of chemical and physical methods. The pure active compounds will be evaluated in other murine tumor systems, viz. B16 melanoma, Ehrlich ascites carcinoma, and Rauscher viral leukemia, for potential use as chemotherapeutic agents in the treatment of human cancer. Mode of action studies will be carried out on the active compounds. Extracts of blue-green algae will also be screened for potential inhibitors of tumor promotion with two bioassays, viz. inhibition of human promyelocytic leukemia (HL-60) cell adhesion by a potent tumor promoter such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and inhibition of specific binding of a potent tumor promoter such as TPA to receptors in a rat embryonic fibroblast cell line (CREF). Several derivatives and analogues of aplysiatoxin, a tumor promoter from the marine blue-green alga Lyngbya majuscula having the same potency as TPA, will be prepared for structure-activity studies and the eventual development of an anti-tumor-promoter (chemopreventitive). Finally antineoplastic agents from certain marine organisms, e.g. palytoxin from the coelenterate Palythoa toxica, will be further evaluated as potential chemotherapeutic drugs.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA012623-12
Application #
3163662
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1977-08-01
Project End
1989-01-31
Budget Start
1985-02-01
Budget End
1986-01-31
Support Year
12
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Hawaii
Department
Type
Schools of Arts and Sciences
DUNS #
121911077
City
Honolulu
State
HI
Country
United States
Zip Code
96822
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Williams, Philip G; Luesch, Hendrik; Yoshida, Wesley Y et al. (2003) Continuing studies on the cyanobacterium Lyngbya sp.: isolation and structure determination of 15-norlyngbyapeptin A and lyngbyabellin D. J Nat Prod 66:595-8
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