Recent developments in the field of cancer genomics have shown transcription factor HIF-1α as a major player in the survival and proliferation of colorectal tumors. Hypoxia targeted drug engineering has led to significant advancements in cancer treatments as a method of directly utilizing the hypoxic regions against the tumor. Novel drug DCQ (2-benzoyl-3-phenyl 6,7-dichloroquinoxaline 1,4-dioxide) has shown promising anti-tumor results in-vitro and in-vivo. The purpose of this study was to utilize a tumor xenograft and genetic mouse model of colorectal cancer to investigate the safety, clinical effectiveness, and mechanism of action of DCQ. Methods: 10 week old Balb/c mice were injected subcutaneously with 2 million CT-26 cells and were monitored for tumor growth over 14 days before receiving treatment. Apcmin/+ mice were clinically evaluated from 8 weeks of age and began treatments at 16 weeks of age. DCQ treatment given at a 17mg/kg dose and 100μL DMSO injection as control. Injections were given bi-weekly over a four week period. Results: DCQ caused significant decrease in tumor weight (p\u3c0.05) and final tumor area (p\u3c0.05) in Balb/c mice at time of sacrifice than control and Apcmin/+ mice showed significantly lower clinical score after 1 week of therapy along with decreased large tumor size (p\u3c0.05) and number (p\u3c0.05). Histological analysis showed increased total apoptotic area (p\u3c0.05) in tumor tissue sections and tumor specific apoptosis in colon tissue in both models. Western blot analysis of Balb/c showed a decreased nuclear expression of HIF-1α (p\u3c0.05) and increased expression of pro-apoptotic genes dephosphorylated-Bad (p\u3c0.001), cleaved caspase-9 (p\u3c0.05), and Bax (p\u3c0.05) paralleled with a decrease in anti-apoptotic Bcl-2 gene (p\u3c0.05). Conclusions: DCQ induces tumor specific apoptosis through mechanisms involving down regulation of HIF-1α and increased intracellular apoptosis in Balb/c mice and Apcmin/+ mice. Novel drug DCQ may potentially have use as a chemotherapeutic agent to reduce the pathology of sporadic intestinal and colorectal cancers
