β-caryophyllene Modulate the Inflammatory and Apoptotic Signally Cascades to Alter the Cellular Response during DMBA Induced Experimental Oral Carcinogenesis; A Histological and In-silico Study

Abstract

β-caryophyllene (BCP) is a more efficient pro-oxidant and anti-cancer property in our previous in-vitro studies. The motivation behind the present examination was to research the anticancer properties of BCP and its molecular mechanism on 7,12-dimethylbenz(a)anthracene (DMBA) treated hamsters. Hamsters were painted with 0.5% DMBA 3 times a week for 10 weeks to developed oral tumor and showed well progressed hyperplasia, dysplasia and differentiated Oral Squamous Cell Carcinoma (OSCC). DMBA alone treated hamster observed 100% tumor formation, elevated tumor incidence, volume and burden, lipid oxidation by-products, diminish antioxidant levels, body weight and imbalance of detoxification enzymes, along with up-regulation of inflammatory (NFҡB, TNF-α, COX-2, iNOS, IL-6), mutant p53, anti-apoptotic (Bcl2) and down regulation of pro-apoptotic (Bax and caspase-9) markers expressions were observed. Oral pre-administration of BCP at different concentration (100, 200 and 400 mg/kg bw) to DMBA-treated hamsters for 14 weeks, completely prevent the OSCC and restored the above biochemical parameters to near normal level, while histological and western blotting investigation were positive support to the biochemical discoveries. These results indicated that BCP potentially inhibit the inflammatory, anti-apoptotic markers and up-regulate the pro-apoptotic markers. Based on our present finding BCP inhibit cancer cell progression and enhances the apoptosis in DMBA induced oral carcinogenesis. In-silico docking investigation was done to supplement the exploratory outcomes.