Naslov
Effect of indomethacin on E-cadherin and β-catenin expression in HT-29 colon cancer cells

Autori
Kapitanović, Sanja ; Čačev, Tamara ; Antica, Mariastefania ; Kralj, Marijeta ; Cavrić, Gordana ; Pavelić, Krešimir ; Spaventi, Radan

Izvornik
Experimental and molecular pathology (0014-4800) 80 (2006), 1; 91-96

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
indomethacin ; colon carcinoma ; HT-29 ; COX-2 ; APC ; beta-catenin ; E-cadherin

Sažetak
Nonsteroidal anti-inflammatory drugs (NSAIDs) lower the incidence of and mortality from colon cancer. Although there is much evidence from epidemiological and laboratory studies that NSAIDs have antitumor activity and reduce the incidence of colon cancer, it's mechanism of action still remains unknown. In this paper, we present the effect of indomethacin on growth inhibition, induction of apoptosis, and alterations in the expression of several genes involved in Wnt signalling in HT-29 colon cancer cells. We have shown that indomethacin reduces the proliferation rate of HT-29 colon cancer cells and induces apoptosis. Concentrations of indomethacin from 10-4 to 10-3 M strongly inhibited the growth of HT-29 cells. The inhibition of growth, as well as induction of apoptosis was dose and time dependent. The tretment of cells with 4 x 10-4 M indomethacin at the concentration which caused strong inhibition of cell growth (about 70%), enhanced expression of APC, decreased expression of beta-catenin and induced expression of E-cadherin proteins. Expression of beta-catenin was not markedly reduced instead beta-catenin was translocated from the nucleus and cytoplasm to the plasma membrane. This results were confirmed by real-time RT-PCR analysis on mRNA level. In the concentration of 4 x 10-4 M indomethacin there was increased expression of APC gene (10.9-fold induction ; delta delta Ct = 3.43) and E-cadherin gene (3.5-fold induction ; delta deltaCt = 1.79). Our results suggest that antiproliferative effect of indomethacin may be contributed to enhanced cell adhesion through increased expression of E-cadherin and translocation of beta-catenin from the nucleus to the cell membrane.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Farmacija

POVEZANOST RADA