Molecular Effect of Betanin on the Molecular Expression Pattern of Cell Proliferative and Inflammatory Signalling Pathways in DMBA‑Induced Oral Carcinogenesis in Hamsters

Background: Cancer development is a sequential process as a result of various cellular adaptation events. Oral cancer (squamous cell carcinoma) is the most predominant variety of head and neck cancer. Betanin (BTN) is isolated from beetroot extracts and is a highly bioavailable antioxidant. BTN exerts a chemopreventive and cytotoxic activity on numerous cancer cells. However, precise identification of the molecules responsible for this tumor‑inhibitory effect is pending. This study aimed to understand the molecular mechanisms underlying the chemopreventive effects of BTN in 7,12‑dimethylbenz (a) anthracene (DMBA)‑induced oral cancer in experimental hamsters. Materials and Methods: The interactions of BTN with antioxidant enzymes, lipid peroxidation, apoptosis, and inflammatory markers in the presence of DMBA were investigated in male golden Syrian hamsters. Results: Oral supplementation of BTN treatment (50 mg/kg BW) daily to oral tumor‑bearing rats successfully prevented DMBA‑induced oral carcinogenesis. Furthermore, BTN administration significantly prevented weight loss and reduced the tumor occurrence, burden, volume, and biochemical parameters such as TBARS, LOOH, SOD, CAT, GPx, GSH, and vitamins E and C. The histological analysis and expression pattern of molecular markers (increased apoptosis (caspase‑3 and 9), proliferative markers (PCNA and Cyclin‑D1), and inflammatory markers (TNF‑α and COX‑2) investigated in hamsters’ buccal mucosa tissues revealed a significant anti‑tumorigenic nature of BTN. Conclusion: The findings of this study show that BTN markedly reduces DMBA‑induced oral cancer in hamsters.