L-Canavanine as a radiosensitization agent for human pancreatic cancer cells |
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Authors: | Bence Aimee K Adams Val R Crooks Peter A |
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Institution: | (1) Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA;(2) Division of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA |
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Abstract: | This study evaluated the in vitro effect of L-canavanine on cell cycle progression in the two human pancreatic cancer cells lines PANC-1 and MIA PaCa-2. After 72 h of exposure to L-canavanine, the percentage of cells in the radiosensitive G2/M phase of the cell cycle increased 6-fold in PANC-1 cells and 4-fold in MIA PaCa-2 cells, when compared to untreated cells. The capacity of L-canavanine to redistribute cells into the G2/M phase of the cell cycle was both concentration- and time-dependent. Since many drugs that cause cells to accumulate in the G2/M phase of the cell cycle are effective radiosensitization agents, the potential of L-canavanine to synergistically enhance the effects of ionizing radiation also was evaluated. The interaction between these treatment modalities was quantified using the median-effect equation and combination index analysis. L-Canavanine was found to be synergistic with radiation when either PANC-1 or MIA PaCa-2 cells were exposed to L-canavanine for 72 h prior to irradiation. These results suggest that L-canavanine in combination with radiation may have clinical potential in the treatment of pancreatic cancer. |
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Keywords: | L-canavanine cell cycle analysis ionizing radiation pancreatic cancer radiosensitization median-effect analysis |
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