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NSAIDs: Painkillers, inflammation inhibitors, anti-cancer drugs and new de-methylating agents
Date:3/26/2008

Researchers at the National Sun Yat-Sen University and Kaohsiung Medical University, Kaohsiung, Taiwan have revealed a new mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) attenuate tumor invasion and metastasis. The research, to be published in the April 2008 issue of Experimental Biology and Medicine, provides new insights for the understanding of the anti-cancer effects of NSAIDs.

NSAIDs have been used for the suppression of pain and inflammation in the clinic for many years. The main targets of these drugs are cyclooxygenases (COXs) which play critical roles in maintaining physiological homeostasis, mediating inflammatory reactions and promoting tumorigenesis. However, COX-independent effects are also important for the inhibition of cancer development by NSAIDs. Indeed, NSAIDs are considered as a novel class of effective chemopreventive drugs.

The research team, led by Wen-Chun Hung, Dean of College of Science, National Sun Yat-Sen University, and a recent doctorial graduate Mei-Ren Pan and two collaborators Hui-Chiu Chang and Lea-Yea Chuang of Kaohsiung Medical University found that NSAIDs up-regulated several anti-metastatic genes including secreted protein acidic and rich in cysteine (SPARC), thrombospindin-1 (TSP-1), TSP-3 and tissue inhibitors of metalloproteinase-2 (TIMP-2) in human lung cancer cells. Our functional assay suggested that increases of SPARC and other anti-metastatic genes were important for NSAIDs to inhibit tumor invasion and metastasis said Wen-Chun Hung. More importantly, we elucidated the underlying mechanism and demonstrated that up-regulation of SPARC in human lung cancer cells was mediated via inhibition of DNA methyltransferases (DNMTs) expression and promoter de-methylation. This is the first report to show that NSAIDs may inhibit the expression of DNMTs to reverse promoter methylation and to reactivate gene transcription.

The researchers say that hypermethylation of tumor suppresso
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Contact: Dr. Wen-Chung Hung
hung1228@ms10.hinet.net
886-752-52000 x5817
Society for Experimental Biology and Medicine
Source:Eurekalert

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