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UBC Theses and Dissertations

In vitro screening of crude extracts and pure metabolites obtained from marine invertebrates for the treatment of breast cancer Stingl, John


Fifteen samples of crude extracts and pure metabolites obtained from marine invertebrates collected from the offshore waters of British Columbia, Papua New Guinea and Sri Lanka had previously been shown to exert cytotoxic activity in the in vitro L1210 leukemic bioassay. For this thesis, these samples were screened for in vitro cytotoxic activity against the drug-sensitive breast tumor cell lines MCF-7, T-47D, ZR-75-1 and MDA-MB-231; the multidrug-resistant and P-glycoprotein (Pgp)-positive breast tumorcell lines MCF-7 Adr and MDA-A1r; 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 withcontrols (ED50), < 25 gg/ml] dose-dependent cytotoxicity against the drug-sensitive cell lines; the ED50 values wereas low as 0.004 gg/ml. Five of the 8 samples exhibited significant cytotoxicity against the multidrug-resistant cell lines; the ED50 values were as low as 0.0006 pg/ml. Incubation of the MCF-7 Adr cells with varying concentrations of compounds in the presence of Adriamycin demonstrated that none of the compounds tested appeared to interfere 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.

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