This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cook, T. Articles by Blumberg, D. Search for Related Content PubMed PubMed Citation Articles by Cook, T. Articles by Blumberg, D.

Nitric Oxide and Ionizing Radiation Synergistically Promote Apoptosis and Growth Inhibition of Cancer by Activating p53

¹ Department of Surgery and ² Center for Biologic Imaging, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania

Nitric oxide (NO) is a potent tumor radiosensitizer; however, its clinical use is limited by systemic side effects. We have demonstrated previously that gene transfer of the human inducible NO synthase (iNOS) gene into tumor cells and tumors induces high-output NO production that significantly enhances tumor radioresponsiveness, with no observed side effects. Notably, iNOS gene transfer enhances tumor radioresponsiveness via apoptotic cell death. Because NO and ionizing radiation are both known to promote p53-dependent apoptosis, we hypothesized that p53 activation might be a primary mechanism for the synergy of these two genotoxic stresses. We report that NO and ionizing radiation synergistically activate p53 in colorectal cancers grown in athymic mice by augmenting phosphorylation of p53 at serine 15. The effect of NO and ionizing radiation on tumor cell apoptosis and tumor radioresponsiveness is significantly reduced in p53 knockout isogenic cancer cell lines. Furthermore, the transfer of both p53 and iNOS genes into tumor cells lacking functional p53 enhanced their radioresponsiveness more than transfer of either gene alone.

This article has been cited by other articles:

				J. S. Isenberg, J. B. Maxhimer, F. Hyodo, M. L. Pendrak, L. A. Ridnour, W. G. DeGraff, M. Tsokos, D. A. Wink, and D. D. Roberts Thrombospondin-1 and CD47 Limit Cell and Tissue Survival of Radiation Injury Am. J. Pathol., October 1, 2008; 173(4): 1100 - 1112. [Abstract] [Full Text] [PDF]

				H. Yasuda, K. Nakayama, M. Watanabe, S. Suzuki, H. Fuji, S. Okinaga, A. Kanda, K. Zayasu, T. Sasaki, M. Asada, et al. Nitroglycerin Treatment May Enhance Chemosensitivity to Docetaxel and Carboplatin in Patients with Lung Adenocarcinoma. Clin. Cancer Res., November 15, 2006; 12(22): 6748 - 6757. [Abstract] [Full Text] [PDF]

				H. Yasuda, M. Yamaya, K. Nakayama, T. Sasaki, S. Ebihara, A. Kanda, M. Asada, D. Inoue, T. Suzuki, T. Okazaki, et al. Randomized Phase II Trial Comparing Nitroglycerin Plus Vinorelbine and Cisplatin With Vinorelbine and Cisplatin Alone in Previously Untreated Stage IIIB/IV Non-Small-Cell Lung Cancer J. Clin. Oncol., February 1, 2006; 24(4): 688 - 694. [Abstract] [Full Text] [PDF]

				A. Goel, C. Gasche, and C. R. Boland Chemoprevention Goes Gourmet: Different Flavors of NO-Aspirin Mol. Interv., August 1, 2005; 5(4): 207 - 210. [Abstract] [Full Text] [PDF]