Scientists uncover NSAIDs mechanism that inhibits tumour invasion

Washington, Mar 27 : A new study from the National Sun Yat-Sen University and Kaohsiung Medical University, Kaohsiung, Taiwan has uncovered a new mechanism by which non-steroidal anti-inflammatory drugs (NSAIDs) reduce tumour invasion and metastasis.

NSAIDs are considered as a novel class of effective chemopreventive drugs.

The main targets of these drugs are cyclooxygenases (COXs), which play a crucial role in maintaining physiological homeostasis, mediating inflammatory reactions and promoting tumour development.

The team led by Wen-Chun Hung, Dean of College of Science, National Sun Yat-Sen University discovered 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 tumour 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," he added.

DNA methyltransferase, a family of enzymes that catalyze the transfer of a methyl group to DNA that serves a wide variety of biological functions.

The researchers said that hypermethylation of tumour suppressor genes is frequently found in many types of human cancer that leads to tumour development.

A number of de-methylating agents have been reported to exhibit potent anti-cancer effects in vitro and in vivo. Therefore, these agents are considered to be useful for cancer therapy.

The study will be published in the April 2008 issue of Experimental Biology and Medicine.

ANI