Abstract 4317: Black raspberries show potent activity in prevention of experimental squamous cell esophageal cancer compared to a combination of selective COX-2 and iNOS inhibitors

Abstract

Abstract Esophageal squamous cell carcinoma (SCC) remains a major health threat worldwide and preventive strategies are needed. We previously reported that overexpression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are correlated with nitrosamine-induced squamous carcinogenesis of the esophagus and the selective iNOS and COX-2 inhibitors significantly inhibit incidence and progression. We also demonstrated anti-cancer activity of black raspberries (BRB) in a rodent model of esophageal SCC. The objective of the current study was to compare the impact of BRB versus the combination of celecoxib, a selective COX-2 inhibitor, and S,S’-1,4-phenylene-bis(1,2-ethanediyl)bis-isothiourea (PBIT), a selective iNOS inhibitor, in inhibition of SCC of the esophagus, and to elucidate molecular mechanism of an effective cancer prevention. We found that BRB is superior to the combination of two drugs in suppression of premalignant tissue growth in the rat esophagi. Moreover, rats fed BRB have lower tumor multiplicity than those fed celcecoxib + PBIT. Our data indicated that BRB also shows a potent inhibitory effect on esophageal iNOS and COX-2, in addition to modulating several associated oncogenic cell signaling pathways. We further conducted parallel mechanistic studies in vitro using BRB anthocyanins and the above two drugs. Our findings demonstrated that dietary BRB is superior to the combination of two chemopreventive pharmaceutical agents in prevention of experimental squamous cell esophageal cancer, suggesting the potential value of additional translational studies in developing food-based products using BRB for the prevention of esophageal SCC carcinogenesis in humans (Supported by NIH/NCI R01 CA131073). Citation Format: Ni Shi, Kenneth M. Riedl, Steven J. Schwartz, Xiaoli Zhang, Steven K. Steven, Tong Chen. Black raspberries show potent activity in prevention of experimental squamous cell esophageal cancer compared to a combination of selective COX-2 and iNOS inhibitors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4317.