Upregulation of NAD(P)H:Quinone Oxidoreductase By Radiation Potentiates the Effect of Bioreductive β-Lapachone on Cancer Cells
| Autor: | Kaoru Terai, Heon Joo Park, Yeon Hee Kook, Doo Sung Lee, David A. Boothman, Jin-Seok Kim, Kyung Hwa Park, In-Mi Ji, Robert J. Griffin, Byung U. Lim, Chang W. Song, Eun Tax Oh, Eun Kyung Choi, Melissa L. Loren |
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| Rok vydání: | 2007 |
| Předmět: |
A549 cell
Cancer Research Programmed cell death p-Lapachone Cell digestive oral and skin physiology Dicoumarol Biology NAD(P)H Dehydrogenase (Quinone) equipment and supplies lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens lcsh:RC254-282 radiation medicine.anatomical_structure Downregulation and upregulation Biochemistry Apoptosis Cancer cell medicine Cancer research A549 cells N001 Bioreductive drug human activities medicine.drug |
| Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 9, Iss 8, Pp 634-642 (2007) |
| ISSN: | 1476-5586 |
| DOI: | 10.1593/neo.07397 |
| Popis: | We found that (β-Lapachone ((β-Lap), a novel bioreductive drug, caused rapid apoptosis, clonogenic cell death in A549 human lung epithelial cancer cells in vitro in a dose-dependent manner. The clonogenic cell death caused by (β-Lap could be significantly inhibited by dicoumarol, an inhibitor of NAD(P)H:quinone oxidoreductase (NO01), also by siRNA for NO01, demonstrating that N001-induced bioreduction of (β-Lap is an essential step in (β-Lap-induced cell death. Irradiation of A549 cells with 4 Gy caused a long-lasting upregulation of N001, thereby increasing N001mediated (β-Lap-induced cell deaths. Although the direct cause of (β-Lap-induced apoptosis is not yet clear, (β-Lap treatment reduced the expression of p53, NF-κB, whereas it increased cytochrome C release, caspase-3 activity, δ2AX foci formation. Importantly, (β-Lap treatment immediately after irradiation enhanced radiation-induced cell death, indicating that (β-Lap sensitizes cancer cells to radiation, in addition to directly killing some of the cells. The growth of A549 tumors induced in immunocompromised mice could be markedly suppressed by local radiation therapy when followed by (β-Lap treatment. This is the first study to demonstrate that combined radiotherapy, (β-Lap treatment can have a significant effect on human tumor xenografts. |
| Databáze: | OpenAIRE |
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