Anti-cancer effects of carnosol in DMBA-induced oral experimental carcinogenesis by oncogenic signaling pathways on in vivo and in silico study.

The most prevalent malignant tumor in the oral cavity, accounting for more than 90% of all oral malignancies, is oral squamous cell carcinoma (OSCC). Therefore, detection or prevention of malignant transformation remains a viable target for the future. Carnosol is a compound derived from rosemary that contains both antioxidant and anti-carcinogens. This study examined the defensive properties of carnosol in DMBA-induced oral carcinogenesis. We have developed the computational based docking analysis to predict the binding affinity and interaction of carnosol with inflammatory and pro-apoptotic proteins. Carnosol was the most potential bioactive compound shows strong binding affinity to low binding energy to bind above the proteins. Following this, we created a hamster model to study buccal pouch carcinogenesis induced by DMBA and assessed buccal tissues using histopathological, biochemical, and western blotting. Carnosol treatment effectively reduced DMBA-induced pathological changes in buccal tissues: Altered detoxification, increased antioxidant levels, and reduced lipid peroxidation enzymes levels. We then examined the impact of carnosol intervention on the modulation of the levels of inflammatory factors and pro-apoptotic markers in oral carcinogenesis. Binding energy was studied between the carnosol between the inflammatory (NF-κB and COX-2) and apoptotic (Bax, caspase-3, and caspase-9) proteins using molecular docking. Our findings suggest that carnosol enhances antioxidant and detoxification levels, potentially prevents oral carcinogenesis by modifying the inflammatory and pro-apoptotic signaling pathways, and acts as an anti-cancer agent.