کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1925323 | 1536364 | 2013 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Reactive oxygen species mediate tolfenamic acid-induced apoptosis in human colorectal cancer cells Reactive oxygen species mediate tolfenamic acid-induced apoptosis in human colorectal cancer cells](/preview/png/1925323.png)
• Tolfenamic acid (TA) induced generation of intracellular ROS.
• TA induced apoptosis and DNA damage to colorectal cancer cells in dependent on ROS.
• TA induced ROS-dependent activation of NF-κB transcriptional activity.
• TA increased ATF3 expression in dependent on ROS and NF-κB activation.
• ROS-mediated DNA damage/NF-κB/ATF3 plays a significant role in TA-induced apoptosis.
Several studies have shown substantial evidences that non-steroidal anti-inflammatory drugs (NSAIDs) exert anticancer effects by generating reactive oxygen species (ROS). Tolfenamic acid (TA) is one of the traditional NSAIDs widely used for treatment of migraine. TA has anti-cancer activities in several human cancer models. In this study, we report that generation of ROS by TA leads to apoptosis through modulation of several pathways in human colorectal cancer cells. TA induced rapid generation of intracellular ROS and led to an increase of phosphorylation of H2AX, a tail moment of comet and distribution of fragmented genomic DNA traces. Treatment of N-acetyl-l-cysteine (NAC) abolished TA-induced phosphorylation of H2AX and apoptosis. Treatment of TA resulted in an increase of nuclear factor-kappaB (NF-κB) transcriptional activity through inhibitor of kappa B (IκB-α) degradation and subsequent p65 nuclear translocation. In addition, TA increased apoptosis-inducing activating transcription factor 3 (ATF3) expression. However, the treatment of NAC abolished TA-mediated NF-κB activation and ATF3 expression and chemical inhibition of NF-κB or knockdown of p65 significantly attenuated TA-induced ATF3 expression. Our finding indicates that ROS-mediated DNA damage and subsequent activation of NF-κB and ATF3 expression plays a significant role in TA-induced apoptosis in human colorectal cancer cells.
Journal: Archives of Biochemistry and Biophysics - Volume 537, Issue 2, 15 September 2013, Pages 168–175