TITLE

Mechanisms by which thiazolidinediones induce anti-cancer effects in cancers in digestive organs

AUTHOR(S)
Okumura, Toshikatsu
PUB. DATE
November 2010
SOURCE
Journal of Gastroenterology;Nov2010, Vol. 45 Issue 11, p1097
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Increasing evidence suggests that thiazolidinediones (TZDs) could have a therapeutic potential for patients with cancers. Here, the evidence on the mechanisms by which TZDs could contribute to different steps of cancer biology in the digestive system is summarized. According to studies, TZDs induce anti-cancer actions through 3 main pathways: (1) cell growth arrest, (2) induction of apoptosis, and (3) inhibition of cell invasion. Cell growth arrest is induced by an increased level of p27. p27 accumulation results from the inhibition of the ubiquitin-proteasome system and/or inhibition of MEK-ERK signaling. TZDs induce apoptosis through increased levels of apoptotic molecules, such as p53 and PTEN and/or decreased level of anti-apoptotic molecules, such as Bcl-2 and survivin. Inhibition of MEK-ERK signaling-mediated up-regulation of E-cadherin and claudin-4, and/or decreased expression of matrix metalloproteinases (MMPs) such as MMP-2 and MMP-9, play a role in the TZD-induced inhibition of cancer cell invasion. Thus, TZDs are capable of inducing anti-tumor action in a variety of ways in gastrointestinal cancers.
ACCESSION #
55128929

 

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