Canolol Inhibits Gastric Tumors Initiation and Progression through COX-2/PGE2 Pathway in K19-C2mE Transgenic Mice

Abstract

4-vinyl-2, 6-dimethoxyphenol (canolol) is an antioxidant phenolic compound extracted from crude canola oil. In current research, K19-C2mE transgenic mice, developing hyperplastic tumors spontaneously in the glandular stomach, were used to study the mechanisms involved in the anti-inflammation and anti-tumor effects of canolol. Tg mice receiving canolol diet had a reduced tumor incidence, to 41.2%, compared with Non-treatment Tg mice, 77.8% of which had gastric tumor (P=0.002). Besides that, the mean tumor diameter was decreased from 6.5mm to 4.5mm (P<0.001) after canolol administration. COX-2/PGE2 pathway is known to play pivotal role in inflammation-induced gastric tumorigenesis. The neutrophils and lymphocytes infiltration was suppressed significantly, and the mRNA levels of the proinflammatory cytokines COX-2, IL-1β and IL-12b were also downregulated in gastric mucosa. Additionally, immunohistochemical analysis showed that COX-2, EP2, Gαs and β-catenin, key factors involving in PGE2 signal transduction, were positive staining with higher H scores in Non-treatment Tg mice, while the expressions were suppressed significantly by 0.1% canolol (P<0.001). In addition, tumor-suppressor miR-7 was reactivated after canolol administration, and COX-2 was showed to be a functional target of miR-7 to suppress the tumor progression. In conclusion, canolol could inhibit the gastritis-related tumor initiation and progression, and the suppression effect was correlated with the blocking up of canonical COX-2/PGE2 signaling pathway and might be regulated by miR-7.

Downregulation of mitochondrial cyclooxygenase-2 inhibits the stemness of nasopharyngeal carcinoma by decreasing the activity of dynamin-related-protein 1

“…Using transgenic mice, Pan et al showed that COX-2/PGE2 promotes lung tumor development via the MAPK pathway, cell proliferation and transformation were inhibited in K-ras/COX-2 -/- mice 36. Another study from Cao et al, using K19-C2mE transgenic mice, revealed that COX-2/PGE2 signal transduction was involved in the initiation and progression of gastric tumors 37. Moreover, overexpression COX-2 was correlated with poor prognosis for breast carcinoma patients 38.…”

Canolol Dimer, a Biologically Active Phenolic Compound of Edible Rapeseed Oil

“…However, at the same time, canolol with a very low concentration (5.6 μM) showed a protective effect against oxidative stress and apoptosis induced by H 2 O 2 in those cells. The newest in vivo research by Cao et al (2015) is in agreement with in vitro antitumor activity of canolol, because canolol diet reduced tumor incidence in K19-C2mE transgenic mice to 41.2% compared with nontreatment transgenic mice, 77.8% of which had gastric tumor. Due to its anti-inflammation and antitumor activity, they concluded that canolol could inhibit the gastritisrelated tumor initiation and progression (Cao et al, 2015).…”

“…The newest in vivo research by Cao et al (2015) is in agreement with in vitro antitumor activity of canolol, because canolol diet reduced tumor incidence in K19-C2mE transgenic mice to 41.2% compared with nontreatment transgenic mice, 77.8% of which had gastric tumor. Due to its anti-inflammation and antitumor activity, they concluded that canolol could inhibit the gastritisrelated tumor initiation and progression (Cao et al, 2015). As there are some differences in the results obtained with various cell lines and possible positive (antioxidant, anticancer, and anti-inflammatory) as well as negative (cytotoxic) effects on cancer cells, but also normal cells, further research on canolol, including more in vivo studies, will surly contribute to safe and proper application of this potent phytochemical in the pharmaceutical and food industry.…”

The protective effects of 18β-glycyrrhetinic acid against inflammation microenvironment in gastric tumorigenesis targeting PGE2-EP2 receptor-mediated arachidonic acid pathway

“…For the grade of COX-2, EP2, Gαs, and β-catenin expression, H score calculation was performed as previously described. 6 …”