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First published on August 3, 2004; DOI: 10.1124/jpet.104.070664

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Received for publication April 29, 2004.
Revised July 12, 2004.
Accepted for publication July 27, 2004.

Selective NSAIDs Induce Thymosin {beta}-4 and Alter Actin Cytoskeletal Organization in Human Colorectal Cancer Cells

Anshu K. Jain 1, Scott M. Moore 1, Kiyoshi Yamaguchi 2, Thomas E. Eling 3*, Seung Joon Baek 2

1 NIEHS 2 University of Tennessee 3 NIH, NIEHS

* Address correspondence to: E-mail: eling{at}niehs.nih.gov

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their anti-inflammatory effects and have been shown to have chemopreventive effects as well. NSAIDs inhibit cyclooxygenase activity to exert their anti-inflammatory effects, but it is not clear whether their anti-tumorigenic ability is through COX inhibition. Using subtractive hybridization, we previously identified a novel member of the TGF-{beta} superfamily that has anti-tumorigenic activity from indomethacin-treated HCT-116 human colorectal cancer cells. On further investigation of this library, we now report the identification of a new cDNA corresponding to the thymosin {beta}-4 gene. Thymosin {beta}-4 is a small peptide which is known for its actin-sequestering function, and it is associated with the induction of angiogenesis, accelerated wound healing, and metastatic potential of tumor cells. However, only selective NSAIDs induce thymosin {beta}-4 expression in a time- and concentration-dependent manner. For example, indomethacin and SC-560 induce thymosin {beta}-4 expression while sulindac sulfide does not. We show that selective NSAIDs induce actin cytoskeletal reorganization, a precursory step to many dynamic processes regulating growth and motility including tumorigenesis. This is the first report to link thymosin {beta}-4 induction with NSAIDs. These data suggest that NSAIDs alter the expression of a diverse number of genes, and provides new insights into the chemopreventive and biological activity of these drugs.


Key words: Colon cancer, Cyclooxygenase, NAG-1, NSAIDs, Thymosin Beta 4, gene expression


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[Abstract] [Full Text] [PDF]


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