The effect of seal oil on paclitaxel induced cytotoxicity and apoptosis in breast carcinoma MCF-7 and MDA-231 cell lines

Wang, Zheyu (2004) The effect of seal oil on paclitaxel induced cytotoxicity and apoptosis in breast carcinoma MCF-7 and MDA-231 cell lines. Masters thesis, Memorial University of Newfoundland.

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Abstract

Studies suggest that ω-3 polyunsaturated fatty acids (PUPAs) are beneficial in inhibiting the growth of cancer cells and may enhance the cytotoxicity induced by certain chemotherapeutic agents. It is known that seal oil is rich in ω-3 PUPAs. The effect of seal oil and its role on the cytotoxicity and apoptosis induced by paclitaxel was, therefore, investigated in breast cancer cell lines, MCF-7 and MDA-MB-231. -- MCF-7 and MDA-MB-231 cells were respectively treated with seal oil, paclitaxel, and paclitaxel in combination with seal oil. Cytotoxicity was evaluated by MTT assay. Apoptosis was investigated by morphological changes and DNA strand break assay. Western blot assay was used to assess the expression of p53 and Bcl-2 proteins. The lipid peroxide products were measured by thiobarbituric acid reactive substances (TEARS) assay and the intracellular lipid composition was determined by gas chromatography (GC). -- MTT assay showed that seal oil induced cell death and enhanced paclitaxel cytotoxicity in both cell lines. The IC₅₀ values of paclitaxel in MCF-7 and MDA-MB-231 cells were reduced 3.3- and 2.4-fold, respectively, by the inclusion of 0.016% seal oil. Morphological assessment and DNA strand break assay indicated that more cells treated with paclitaxel in combination with seal oil underwent apoptosis than that with paclitaxel alone treatment. Seal oil alone was also found to induce apoptosis in both cell lines. Western blot showed that the expression of apoptosis inhibitor Bcl-2 protein in both cell lines was down-regulated by seal oil and was inhibited further when cells were treated with paclitaxel in combination with seal oil. GC assay determined that the total PUFAs increased significantly in the intracellular lipid composition following incubation with seal oil, which may be responsible for the increased lipid peroxides found in cells incubated under the same conditions. -- In addition to seal oil, Intralipid®, which is a soybean oil emulsion mainly containing ω-6 PUFAs, was also studied for its cytotoxicity and apoptosis induction. It was found that soybean oil induced cell death in the MCF-7 cell line but promoted cell growth in the MDA-MB-231 cell line. Soybean oil did not induce apoptosis as characterized by morphological assessment. -- In conclusion, seal oil was found to induce apoptosis, and to enhance the cytotoxicity and apoptosis induced by paclitaxel in both breast cancer cell lines, which may be due to its ability to down-regulate the expression of Bcl-2 protein and to produce lipid peroxides. The beneficial effect exerted by seal oil suggests that seal oil may have a great potential in the management of cancer.

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