292 Mechanistic Studies On the Anti-Cancer Activity of 2,4-disulfonyl-PBN (OKN-007) Robert a Floyd 1 , Hema Chandru 1 , Charles Stewart 1 , and Rheal a Towner 1 1 Oklahoma Medical Research Foundation Sulf2 resides in the extracellular matrix of cancer cells and enzymatically removes sulfate from the 6-O-sulfate esters of heparin. Several tumors have been shown to be enriched in Sulf2 in comparison to normal tissues where its levels is either absent or present at very low levels. Sulf2 action alters growth factor binding to the extracellular matrix of cells and has been shown to be important in the development of cancers of breast, lung, liver, colon, and pancreas as well as other cancers. Sulf2 mobilizes fibroblast growth factors (FGFs), vascular endothelial growth factor (VEGF) and stromal derived growth factor-1 (SDF-1) bound to heparin. We found that OKN-007 acts to weakly inhibit the aryl sulfatase activity of Sulf2 acting on the substrate 4- methylumbelliferyl-sulfate (4-MUS) and to more effectively inhibit the enzymatic activity of Sulf2 when it acts upon its natural substrate the 6-O-sulfate ester of heparin. the Sulf2 enzymatic activity was potently inhibited by suramin, a compound that has 6 phenyl-sulfonyl groups as a part of it chemical structure and has been shown to have anti-cancer activity. Utilizing the natural substrate we have shown that other sulfonyl-phenyl compounds act to suppress the activity of Sulf2. We have conducted preliminary studies to see if OKN-007 has anti-cancer activity in a breast cancer mouse xenograph model. Balb/c female ovariectomized Estradiol pellet-implanted nude mice were implanted with MCF-7 breast cancer cells and OKN-007 was administered at 250mg/kg/day in the drinking water. the experiment was terminated at week 5 at which time the data showed that OKN-007 decreased the average tumor volume by 33%. OKN-007 has been shown to have anti-cancer activity in the rat C6 model of glioma. the anti-cancer mechanism of action of OKN-007 is still unknown. Recently we have explored the potential of OKN-007 to alter cancer cell movement experienced in a gradient involving the chemokine (CXCL12) and its cellular receptor CXCR4. the CXCL4/CXXL12 gradient is considered to be important in the metastasis of primary cancers. Preliminary results with rat C6 glioma cells, U87MG human glioma cells as well as MCF-7 breast cancer cells indicate that OKN-007 at low concentrations inhibits cancer migration in a CXCR4/CXCL12 gradient. These preliminary observations need to be explored in more depth. Research supported in part by US Army Concept Grant W81XWH-09-1-0352. Dr. Floyd holds the Merrick Foundation Chair in Aging Research. doi:10.1016/j.freeradbiomed.2011.10.316 293 Oxidative Stress Induction and Antitumor Activity of Association of Sodium Orthovanadate and Ascorbic Acid Tânia T.M.F Günter 1 , Carla Crystyne Baron 1 , Karina Bettega Felipe 1 , Mirelle Sifroni Farias 1 , Valdelúcia M. A. S. Grinevicius 1 , Fabiana Ourique 1 , Nadia F Bücher 1 , Rozangela Curi Pedrosa 1 , and Reginaldo Geremias 2 1 Department of Biochemistry, Federal University of Santa Catarina, Florianópolis, Brazil, 2 Department of Rural Sciences, Federal University of Santa Catarina, Curitibanos, Brazil Objective: This work evaluated the in vivo antitumor effect of sodium orthovanadate(SO), sodium ascorbate(SA) and sodium orthovanadate-sodium ascorbate(SO/SA) association as well verified the potential relationship with free radicals generation. Methods: Antitumor activity was investigated using the Ehrlich ascites carcinoma (EAC) inoculated intraperitoneally (day zero) in Balb/c mice (18-20g b.w.,n=6). They received daily intraperitoneally: NaCl 0.9% (50μL;Negative Control;NC), Doxorrubicin (1.2mg/kg; Positive Control=PC) and treated groups SO, SA, SO/SA(18.75; 187.50; 18.75/187.50mg/kg, respectively). the treatments lasted 9 days. On 10 th day all animals were sacrificed and ascitic fluid was collected, abdominal circumference (AB), ascitic liquid volume (ALV) and tumor growth inhibition (TGI) were assessed as well catalase and superoxide dismutase activity. Results: PC,SO and SO/SA reduced AB (0.3±0.1; 1.6±0.3; 0.9±0.5cm), ALV (0.0;7.1±0.5;3.5±1.8mL) respectively, compared to NC (3.5±0.6cm; 11.0±0.7mL;0.0%) and SA(3.1±0.8cm; 4.5±3.1mL; 69.6±11.3%) and increased TGI (91.3±0.2;45 1±9.7; 73.7±11.3%) showing an antitumor potential. There was increased SOD activity (SA=24.3±13.1USOD/mg protein;SO=63.4±17.0;SO/SA=30.2±12.2) compared to NC(19.2±8.9USOD/mg protein).The apoptotic cells number (flow cytometry) increased after treatment with SO/SA(31.6%) compared to NC, SA and SO(17.1; 1.54; 5.5%). Furthermore the staining with ethidium bromide/acridine orange showed the percentage of unviable cells (SA=3.6;SO=17.7;SO/SA=38.7%) in relation to NC(2.4%). Conclusion: the results suggest that SO/SA exhibited antitumor activity and it also caused induction of oxidative stress. These findings can indicate a possible SO/SA antitumor action mechanism. Keywords: sodium orthovanadate, sodium ascorbate, antitumor effect, Ehrlich ascites carcinoma doi:10.1016/j.freeradbiomed.2011.10.317 294 Oxidative Stress Induction and Antitumor Activity of Croton Celtidifolius Baill Against the Ehrlich Ascites Carcinoma Mirelle Sifroni Farias 1 , Fernanda Biscaro 1 , Karina Bettega Felipe 1 , Tânia M. Fischer Günter 1 , Nadia Cristina Falcão Bücher 1 , Carla Crystyne Baron 1 , Maicon Kviecinski 1 , Fabiana Ourique 1 , Eduardo Benedetti Parisotto 1 , Valdelúcia M. A. S. Grinevicius 1 , Rozangela Curi Pedrosa 1 , and Reginaldo Geremias 2 1 Department of Biochemistry, Federal University of Santa Catarina, Florianópolis, Brazil, 2 Department of Rural Sciences, Federal University of Santa Catarina, Curitibanos, Brazil Objective: the aim of this work was to evaluate the in vivo antitumor potential of this Croton celtidifolius latex and verify if this activity is related to the ability of latex to generate free radicals. Methods: Antitumor activity of was investigated using the Ehrlich ascites carcinoma (EAC) inoculated intraperitoneally in isogenic Balb/c male mice (±20g g body weight). the inoculation moment was used to elect the day 0. After 24h of inoculation, animals were divided into two groups (n=6): Negative Control (NC), which received only saline (50μL at 0.9 %) and the treated group (TG) which received latex from Croton celtidifolius (3.2 mg/ kg body weight). the experimental treatment lasted 9 days and on the tenth day animals were sacrificed and the ascitic fluid was collected for the study. the following parameters were assessed: tumour growth inhibition, determining the cell death type induced (incorporation of annexin V and propidium iodide), as well as lipoperoxidation (TBARS) and activity of superoxide dismutase (SOD). Results were expressed by means and standard deviations and were analyzed using one-way ANOVA and Tukey- Kramer test. a p-value<0.05 was considered statistically significant. Results: the evaluations indicated that the treatment with latex caused significantly increased the number of apoptotic cells (NC= 3.13%; TG = 47.47%), lipoperoxidation (NC= 0.0062±0.003 SFRBM 2011 S122