| Summary: | <p>Abstract</p> <p>Background</p> <p>Reactive oxygen species (ROS) are intricately involved in tumor progression through effects on proliferation, apoptosis and metastasis. But how ROS works is not well understood. In previous study, we found PUMA (p53-upregulated modulator of apoptosis) played an important role in oxaliplatin-induced apoptosis. In the present study, we detect the role of PUMA in H<sub>2</sub>O<sub>2</sub>-induced apoptosis in colorectal cancer cells and investigate the potential mechanism.</p> <p>Methods and results</p> <p>We showed that H<sub>2</sub>O<sub>2 </sub>stimulated the activity of a 493 PUMA promoter reporter gene construct. Suppressing the expression of PUMA abrogated H<sub>2</sub>O<sub>2</sub>-induced apoptosis. Deletion of the Sp1-binding sites also decreased the transactivation of PUMA promoter by H<sub>2</sub>O<sub>2</sub>. Furthermore, induction of PUMA promoter activity by H<sub>2</sub>O<sub>2 </sub>was abrogated by PFT-α (a p53 inhibitor) and Mithramycin A (a Sp1 inhibitor), as compared with PFT-α alone. To determine the effects of Sp1 on PUMA in H<sub>2</sub>O<sub>2</sub>-induced apoptosis, procaspase 3, procaspase 9 and procaspase 8 expression was assessed. Mithramycin A and PFT-α also reduced H<sub>2</sub>O<sub>2</sub>-induced apoptosis synergistically and abrogated the expression of procaspase 3 and procaspase 9.</p> <p>Conclusion</p> <p>Our findings suggest that PUMA plays a role in H<sub>2</sub>O<sub>2</sub>-induced apoptosis, and that Sp1 works together with p53 in the regulation of H<sub>2</sub>O<sub>2</sub>-induced PUMA expression and apoptosis in colorectal cancer cells. This study provides important regulatory insights in the mechanisms of ROS in colorectal cancer.</p>
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