Anti-proliferative effects of γ-tocotrienol on mammary tumour cells are associated with suppression of cell cycle progression |
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Authors: | G. V. Samant V. B. Wali P. W. Sylvester |
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Affiliation: | College of Pharmacy, University of Louisiana at Monroe, Monroe, LA, USA |
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Abstract: | Objectives: Previous studies have shown that γ-tocotrienol induces potent anti-proliferative effects on +SA mammary tumour cells in culture; here, investigations have been conducted to determine its effects on intracellular signalling proteins involved in regulating cell cycle progression. Materials and methods: +SA cells were maintained in mitogen-free defined media containing 0 or 4 μ m γ-tocotrienol, for 48 h to synchronize cell cycle in G0 phase, and then they were exposed to 100 ng/ml EGF to initiate cell cycle progression. Whole cell lysates were collected at various time points from each treatment group and were prepared for Western blot analysis. Results and conclusions: Treatment with 4 μ m γ-tocotrienol significantly inhibited +SA cell proliferation over a 4-day culture period. Moreover, this treatment resulted in a relatively large reduction in cyclin D1, cyclin dependent kinase (CDK)4, CDK2 and CDK6 levels, between 4 and 24 h after EGF exposure. Tocotrienol treatment also resulted in a relatively large increase in CDK inhibitor (CKI) p27, prior to and after EGF exposure, but had little effect on levels of CKIs, p21 and p15. Tocotrienol treatment also induced a large relative reduction in retinoblastoma (Rb) protein phosphorylation at ser780 and ser807/811. These findings strongly suggest that anti-proliferative effects of γ-tocotrienol are associated with reduction in cell cycle progression from G1 to S, as evidenced by increased p27 levels, and a corresponding decrease in cyclin D1, CDK2, CDK4, CDK6 and phosphorylated Rb levels. |
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