Renteria O1, Gao X2 and Huerta S1,2*
1Dallas VA Medical Center, Dallas Texas, USA
2University of Texas Southwestern at Dallas, Texas, USA
Background: Nitric oxide (NO) donors have demonstrated radiosensitizing activity against colorectal cancer in vitro and in vivo. JS-K is an NO donor that releases NO upon activation by glutathione. We evaluated the activity of JS-K in vitro and in vivo against HT-29 cells.Methods: Cell survival was assessed by colony forming assays in cells subjected to ionizing radiation (IR) [0 - 6 Gray (Gy)] with and without JS-K [0.5 μM]. Mice were inoculated with HT-29 cells and randomized to four treatments: (1) control, (2) IR [2 Gy X 5], (3) JS-K [20 μmol/Kg i.p.], (4) JS-K+ IR.Results: JS-K-treated cells were more sensitive to IR (SF-4 = 0.35) vs. untreated cells (SF-4 = 0.45) and (SF-6 = 0.21 vs. 0.29; respectively). Following 34 days of treatment, the JS-K+IR xenografts had a 9.4% reduction of tumor growth (p≤ 0.001) and at 40 days a 14.3% decrease compared to control (p≤ 0.0001). Western blot analysis showed an increase in cleaved PARP-1 and AIF with a concomitant decrease in Bcl-2.Conclusion: JS-K demonstrated antitumor activity against HT-29 cells in vitro and in vivo. Caspase and non-caspase mediated mechanisms of apoptosis were involved in this response.
Nitric oxide donor; Rectal cancer; Complete pathological response
Renteria O, Gao X, Huerta S. Radiosensitization of HT-29 Colorectal Cells and Xenografts by the Nitric Oxide Donor JS-K. Clin Surg. 2016; 1: 1162.