Abstract
BackgroundReactive 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.Methods and resultsWe showed that H2O2 stimulated 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 H2O2 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 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.ConclusionOur 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.
Highlights
A large body of evidence indicates that Reactive oxygen species (ROS) plays a central role in intracellular and intercellular signal transduction pathway in a variety of cellular process
Our findings suggest that p53 upregulated modulator of apoptosis (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
We found that PUMA plays a role in H2O2-induced apoptosis in colorectal cancer cells
Summary
A large body of evidence indicates that ROS plays a central role in intracellular and intercellular signal transduction pathway in a variety of cellular process. ROS are capable of activating certain transcription factors directly and thereby modulating the regulation of gene transcription. Several transcriptional factors such as AP1, Sp1 [2,3], Smad [4] and snail are potentially associated with ROS-triggered cellular process. Apoptosis and cancer are opposed phenomena but ROS have been widely reported to play a key role in both[5,6], suggesting that the regulation of gene expression by oxi-. Reactive oxygen species (ROS) are intricately involved in tumor progression through effects on proliferation, apoptosis and metastasis. We detect the role of PUMA in H2O2-induced apoptosis in colorectal cancer cells and investigate the potential mechanism
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call