Sesamol suppresses cyclooxygenase-2 transcriptional activity in colon cancer cells and modifies intestinal polyp development in ApcMin/+ mice

Abstract

Excessive prostaglandin production by cyclooxygenase-2 in stromal and epithelial cells is a causative factor of colorectal carcinogenesis. Thus, compounds which inhibit cyclooxygenase-2 transcriptional activity in colon epithelial cells could be candidates for anti-carcinogenic agents. A cyclooxygenase-2 transcriptional activity in the human colon cancer cell line DLD-1 has been measured using a β-galactosidase reporter gene system. Using this system, we demonstrated that the decrease in basal cyclooxygenase-2 transcriptional activities at 100 µM sesamol, one of the lignans in sesame seeds, was 50%. Other compounds in sesame seeds such as sesamin, sesamolin, ferulic acid, and syringic acid did not exhibit significant suppression of cyclooxygenase-2 transcriptional activity at up to 100 µM. In a following experiment, 6-week-old male Min mice, Apc-deficient mice, were divided into a non-treated and 500 ppm sesamol groups. At the age of 15 weeks, it was found that treatment with sesamol decreased the number of polyps in the middle part of small intestine to 66.1% of the untreated value. Moreover, sesamol suppressed cyclooxygenase-2 and cytosolic prostaglandin E2 synthase mRNA in the polyp parts. The present findings may demonstrate the novel anti-carcinogenetic property of sesamol, and imply that agents that can suppress cyclooxygenase-2 expression may be useful cancer chemopreventive agents.

Theracurmin inhibits intestinal polyp development in Apc‐mutant mice by inhibiting inflammation‐related factors

“…In our previous report using Min mice, cancer chemopreventive agents mainly suppressed intestinal polyp development less than 1.5 mm in a diameter . Thus, our data are consistent with our previous data.…”

Sesamol induces mitochondrial apoptosis pathway in HCT116 human colon cancer cells via pro-oxidant effect

“…Its anti-inflammation character was detected as suppression of basal COX-2 transcriptional activity in mice colon cancer (DLD-1 cells) [8]. Black sesame seed extract was found to induce apoptosis in HT-29 colon cancer [9].…”

Critical Dietary Factors in Cancer Chemoprevention

“…We have shown the suppressive potential of sesamol on intestinal polyp development in Min mice (Shimizu et al 2014). The administration of 500 ppm sesamol reduced the total number of intestinal polyp development compared with that of the untreated group.…”

“…In our experiments, among the four sesame seed constituents (ferulic acid, sesamin, sesamol, and sesamolin), 100 μM sesamol treatment in a human colon cancer cell line, DLD-1 cells, for 48 h suppressed basal cyclooxygenase-2 (COX-2) promoter transcriptional activity as detected by a β-galactosidase reporter gene system (Mutoh et al 2000;Shimizu et al 2014). COX-2 is an inducible enzyme to produce PGE 2 , and both COX-2 expression and PGE 2 levels are increased in colon carcinoma tissues compared with that of normal colonic mucosa.…”