L-Canavanine as a radiosensitization agent for human pancreatic cancer cells.
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.
Bence
Aimee K
AK
Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
Adams
Val R
VR
Crooks
Peter A
PA
D002172:Canavanine / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D008956:Models, Chemical; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D011839:Radiation, Ionizing; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D013997:Time Factors
D011838:Radiation-Sensitizing Agents; D002172:Canavanine