INVITRO SCREENING OF CRUDE EXTRACTS AND PURE METABOLITES OBTAINED FROM MARINE-INVERTEBRATES FOR THE TREATMENT OF BREAST-CANCER

A total of 15 samples (crude extracts and pure secondary metabolites) obtained from marine invertebrates collected from the offshore waters of British Columbia, Papua New Guinea, and Sri Lanka have previously been shown to exert cytotoxic activity in the in vitro L1210 leukemic bioassay. We screened these metabolites for in vitro cytotoxic activity against the drug-sensitive breast-tumor cell lines MCF-7, T-47D, ZR-75- 1, and MDA-MB23 1; the multidrug-resistant and P-glycoprotein (Pgp)-positive breast-tumor cell lines MCF-7 Ad(r) and MDA-Al(r); and normal and malignant human breast epithelial cells (HBEC) in primary culture. Eight samples exhibited significant [drug concentration resulting in a 50% decrease in cell growth as compared with controls (ED50), <25-mu-g/ml] dose-dependent cytotoxicity against the drug-sensitive cell lines; the ED50 values were as low as 0.004-mu-g/ml. Five of the eight samples exhibited significant cytotoxicity against the multidrug-resistant cell lines; the ED50 values were as low as 0.0006-mu-g/ml. Incubation of MCF-7 Ad(r) cells with varying concentrations of compounds in the presence of Adriamycin demonstrated that none of the compounds tested interfered with Pgp function. Results obtained using HBEC in primary culture showed a wide range of chemosensitivities for a given drug against tissue taken from different patients, demonstrating the uniqueness of the response of different individuals to chemotherapy.