Sp1 is involved in H₂O₂-induced PUMA gene expression and apoptosis in colorectal cancer cells

• Main Authors: Wang Jide, Geng Yan, Lin Shiyong, Wang Jing, Wang Xinying, Jiang Bo
• Format: Article
• Language: English
• Published: BMC 2008-09-01
• Series: Journal of Experimental & Clinical Cancer Research
• Online Access: http://www.jeccr.com/content/27/1/44

<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 H₂O₂-induced apoptosis in colorectal cancer cells and investigate the potential mechanism.</p> <p>Methods and results</p> <p>We showed that H₂O₂stimulated the activity of a 493 PUMA promoter reporter gene construct. Suppressing the expression of PUMA abrogated H₂O₂-induced apoptosis. Deletion of the Sp1-binding sites also decreased the transactivation of PUMA promoter by H₂O₂. Furthermore, induction of PUMA promoter activity by H₂O₂was 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 H₂O₂-induced apoptosis, procaspase 3, procaspase 9 and procaspase 8 expression was assessed. Mithramycin A and PFT-α also reduced H₂O₂-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 H₂O₂-induced apoptosis, and that Sp1 works together with p53 in the regulation of H₂O₂-induced PUMA expression and apoptosis in colorectal cancer cells. This study provides important regulatory insights in the mechanisms of ROS in colorectal cancer.</p>