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Investigation of the effect of a novel vitamin E derivative (alpha-TEA) alone and in combination with a known chemotherapuetic agent in human breast cancer using cell culture and animal models

by Lawson, Karla Ann.

Abstract (Summary)
A non-hydrolyzable ether analog of RRR-?-tocopherol, 2,5,7,8-tetramethyl-2R- (4R, 8R, 12-trimethyltridecyl)chroman-6-yloxyacetic acid (called RRR-?tocopheryloxyacetic acid or RRR-?-tocopherol ether-linked acetic acid analog and abbreviated ?-TEA) exhibits anti-tumor activity in vitro and in vivo using a syngeneic Balb/c mouse mammary tumor model (line 66 clone 4 stably transfected with green fluorescent protein; 66c1-4-GFP). Treatment of cells with 5, 10, or 20 µg/ml of ?-TEA for 3 days produced 6, 34 and 50% apoptosis, respectively; and treatment of cells with 10 µg/ml for 2, 3, 4 and 5 days produced 20, 35, 47 and 58% apoptosis, respectively. A liposomal formulation of ?-TEA administered by aerosol reduced subcutaneous tumor growth and lung metastasis. ?-TEA treated animals showed a significant decrease in tumor volumes over 17 days of aerosol treatment (p < 0.001). 40% of aerosol, as well as untreated control mice, had visible, macroscopic lung metastases versus none (0%) of the ?-TEA treated mice. Based on fluorescence microscopic examination of the surface (top and bottom) of flattened whole left lung lobes, an average of 60 ± 15 and 102 ± 17 versus 11 ± 4 fluorescent microscopic metastases were observed in aerosol control and untreated control versus ?-TEA treated animals, respectively. ??TEA formulated in ethanol + peanut oil (5 mg/mouse/day) delivered by gavage did not reduce subcutaneous primary tumor burden; however, fluorescent microscopic lung metastases were significantly reduced (p < 0.0021). In summary, ?-TEA formulated in liposomes and delivered by aerosol is a potent anti-tumor agent and reduces lung metastasis. 19
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School:The University of Texas at Austin

School Location:USA - Texas

Source Type:Master's Thesis

Keywords:vitamin e cancer cells tumors

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