Influence of COX-inhibitors on the localization of PKC δ in the small intestine of the APC gene defect mice

Abstract

According to Fearon and Vogelstein, the process of malignant transformation in intestinal cells is caused by stepwise gene mutations with phenotypic adenoma-carcinoma-sequence. COX inhibitors show tumorsuppressive effects both in vitro and in vivo. Since intestinal tumors of humans, rats and mice show overexpression of the COX-2 isoenzyme, the specific inhibition of COX-2 is considered to be a basic mechanism of tumor prevention. Protein kinase C (PKC) family plays an important role in signal transduction. PKCS isoenzyme is reported to be involved in cell differentiation and apoptosis onset. To investigate changes in PKCS expression and distribution under APC gene defect and COX-2 inhibition, we used the MIN-mouse model. Mice were treated with three different COX-inhibitors of various specificity over 60 days against control. Piroxicam, Sulindac, and Meloxicam were administered with drinking water in adequate doses. Formalin-fixed samples of the small intestine were investigated by indirect immunohistochemistry with antibodies against PKCS. Both in untreated and in Balb C mice, rare positive signals of PKCS were found mainly at the luminal surface of the villi. The cellular distribution was ubiquitous in the cytoplasm. In contrast, a distinct nuclear immunoreactivity was found under COX inhibition. PKCS immunoreactivity seemed to increase with COX-2 inhibitor specificity. These results corresponded with increased apoptotic activity (TUNEL, KLENOW) in the intestinal tissue after treatment with COX inhibitors. Considering that the translocation of PKCG from the cytosol to membrane structures and nucleus is a sign of its activation, a role for this isoenzyme in the regulation of the anticarcinogenic effects of COX-2 inhibition is to be concluded.

Evaluating the use of resistant starch as a beneficial dietary fiber and its effect on physiological response of glucose, insulin, and fermentation

“…Research studies utilizing RS cover a wide scope of interest including digestion rates and bioavailability Fässler et al, 2006b;Granfeldt et al, 1993;Hoebler et al, 1999;Holm and Björck, 1992); product development and sensory evaluation 1 (Aigster et al, 2011;Baixauli et al, 2008;Maziarz et al, 2013); incorporation or efficacy of RS as a functional ingredient ; metabolic responses and health benefits Heijnen et al, 1995;; and other aspects. Test species in these studies have included rats (Bauer-Marinovic et al, 2006;Perrin et al, 2001), pigs (Giuberti et al, 2013), and humans (Worthley et al, 2009); in additions, observations have been made in vivo and in vitro when assessing certain attributes such as physiological responses of glucose, insulin, and fermentation van Munster et al, 1994a;. Furthermore, scientific evaluation of the benefits of RS has also generated commercial interest.…”