The involvement of endoplasmic reticulum stress in the suppression of colorectal tumorigenesis by tolfenamic acid.

ABSTRACT: The nonsteroidal anti-inflammatory drug tolfenamic acid has been shown to suppress cancer cell growth and tumorigenesis in different cancer models. However, the underlying mechanism by which tolfenamic acid exerts its antitumorigenic effect remains unclear. Previous data from our group and others indicate that tolfenamic acid alters expression of apoptosis- and cell-cycle arrest-related genes in colorectal cancer cells. Here, we show that tolfenamic acid markedly reduced the number of polyps and tumor load in APC(min)(/+) mice, accompanied with cyclin D1 downregulation in vitro and in vivo. Mechanistically, tolfenamic acid promotes endoplasmic reticulum (ER) stress, resulting in activation of the unfolded protein response (UPR) signaling pathway, of which PERK-mediated phosphorylation of e

SUBMITTER: Zhang X 

PROVIDER: S-EPMC3855893 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature