Nonsteroidal anti-inflammatory drugs and oxidative stress in cancer cells
M. Adachi1,2, H. Sakamoto2, R. Kawamura2, W. Wang1,2, K. Imai1 and Y. Shinomura1
1First Department of Internal Medicine and 2Division of Applied Molecular Oncology, Graduate School of Medicine, Sapporo Medical University, Sapporo, Japan.
Offprint requests to: Masaaki Adachi, M.D. & Ph.D, The First Department of Internal Medicine, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan. e-mail: adachi@sapmed.ac.jp
Summary. Nonsteroidal antiinflammatory drugs (NSAIDs) induce apoptosis in a variety of cancer cells, including those of colon, prostate, breast and leukemia. In addition, the classical NSAIDs sulindac and aspirin are promising chemopreventive agents against colon cancer. NSAIDs inhibit cyclooxygenases (COX) preventing the formation of prostaglandins, prostacyclin and thromboxane. NSAIDs also exert other biological effects, including generation of reactive oxygen species (ROS) and inhibition of NF-kappaB-mediated signals. Despite many suggested mechanisms for their anticancer effects, it remains uncertain how they induce cell cycle arrest and apoptosis in cancer cells. Furthermore, there is little information on the selectivity of NSAIDs-mediated anticancer effects, although this is one of the most important issues in cancer therapy. Increased understanding of the biological basis for the anticancer activity of NSAIDs and their selectivity is essential for future therapeutic advances. In this paper, we propose that increased ROS generation is one of the key mechanisms for NSAIDs-mediated anticancer effects on various cancer cells. Histol Histopathol 22, 437-442 (2007)
Key words: NSAIDs, ROS, DNA damage
DOI: 10.14670/HH-22.437