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Alpha Tocopheryl Succinate, Retinoic Acid and Polar Carotenoids Enhanced the Growth-Inhibitory Effect of a Cholesterol-Lowering Drug on Immortalized and Transformed Nerve Cells in Culture

Bipin Kumar, MD, William C. Cole, PhD and Kedar N. Prasad, PhD

Center for Vitamins and Cancer Research, Department of Radiology, University of Colorado Health Sciences Center, Denver, Colorado



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Fig. 1A. Effect of mevastatin on the growth of mouse neuroblastoma (NBP2) cells and rat immortalized non-tumorigenic dopamine (DA) neurons, 1 RB3AN27 (N27) in culture. Cells were plated in a 24-well chamber and compounds were added 24 hours later. Cell viability was determined after three days of treatment. Each experiment was repeated three times with triplicate samples. Error bars are 95% confidence intervals. 1B. High performance liquid chromatography (HPLC) profile of pravastatin (P, open-ring structure) and mevastatin (M, closed-ring structure) indicating distinct peaks.

 


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Fig. 2. Effect of antioxidants on the growth of mouse neuroblastoma (NBP2) cells (A) and rat immortalized non-tumorigenic dopamine (DA) neurons (B), 1 RB3AN27 (N27) in culture. Cells were plated in a 24-well chamber and d-{alpha}-tocopheryl succinate ({alpha}-TS), 13-cis-retinoic acid and polar carotenoids, or an equivalent amount of their solvent, were added separately 24 hours later. Cell viability was determined after three days of treatment. Each experiment was repeated three times with triplicate samples. Error bars are 95% confidence intervals.

 


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Fig. 3. Effect of mevastatin in combination with various concentrations of individual antioxidant on the growth of mouse neuroblastoma (NBP2) cells (A) and rat immortalized non-tumorigenic dopamine (DA) neurons (B), 1 RB3AN27 (N27) in culture. Cells were plated in a 24-well chamber and mevastatin (25.6 µM for NB cells and 5.12 µM for N27 cells) together with various concentrations of d-{alpha}-tocopheryl succinate ({alpha}-TS), 13-cis-retinoic acid and polar carotenoids were added immediately after one another. Cell viability was determined after three days of treatment. Each experiment was repeated three times with triplicate samples. Error bars are 95% confidence intervals (C.I.). Dotted lines show the 95% C.I. for the mevastatin response alone.

 





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