-Gingerol impedes 7,12-dimethylbenz(a)anthracene-induced inflammation and cell proliferation-associated hamster buccal pouch carcinogenesis through modulating Nrf2 signaling events.
J Biochem Mol Toxicol. 2021 Apr ;35(4):e22689. Epub 2020 Dec 21. PMID: 33347680
The present study examines the chemopreventive role of -gingerol, an active component of ginger, on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis models. The HBP has been developed with an addition of 0.5% of DMBA to the HBP area three times per week, up to the end of the 16th experimental week. At the end of the experiment, we noticed 100% tumor incidence and precancerous lesions, such as dysplasia, hyperplasia, keratosis, and well-differentiated squamous cell carcinoma, in DMBA-induced HBP. Furthermore, we observed that -gingerol inhibited the increased thiobarbituric acid-reactive substances and decreased antioxidant levels in DMBA-induced hamsters. Moreover, -gingerol inhibits DMBA-exposed over expression of inflammatory markers (inducible nitric oxide synthase, interleukin [IL]-1β, IL-6, cyclooxygenase-2, and tumor necrosis factor-α) and cell proliferation markers (cyclin D1, proliferating cell nuclear antigen); induces proapoptotic markers in HBP. Nuclear factor erythroid-2-related factor-2 (Nrf2) is a major antioxidant transcription factor, which regulates the antioxidant gene-dependent scavenge of tumor proliferation and apoptosis. Overexpression of Nrf2 signaling plays a pivotal role and can be a novel target in preventing carcinogenesis. In this study, -gingerol restores the DMBA-induced depletion of Nrf2 signaling and thereby prevents buccal pouch carcinogenesis in hamsters. These results point out that -gingerol impedes the responses of inflammatory andcell proliferation-associated progression of cancer through the action of Nrf2 signaling.