Lycorine impedes 7,12-dimethylbenz(a)anthracene exposed hamster oral carcinogenesis through P13K/Akt and NF-κB inhibition

Abstract

Abstract Objectives Oncogenic signaling pathways that are activated abnormally play a key activity in tumor initiation and development. This research aimed to examine the preventive efficiency of lycorine in the buccal pouch hamster tumor model based on its capacity to target phosphoinositide 3-kinase (PI3K)/Akt and nuclear factor-kappa B (NF-κB) signaling cascades. Methods The induction of oral tumor in male golden Syrian hamsters was done by 7,12-dimethylbenz [a] anthracene (DMBA) painting on the left buccal pouch thrice a week for 10 weeks. The chemopreventive effect of lycorine (20 mg/kg b.w.) was assessed by treating orally for 14 weeks of the experimental period. The biochemical endpoints such as lipid peroxidation (LPO), antioxidants, and phase I and II detoxification agents were analyzed. Results The treatment of lycorine to DMBA-induced hamsters drastically suppressed tumor incidence and tumor size and reverted the levels of the biochemical indicator. Moreover, lycorine significantly downregulated the p53, Cyclooxygenase 2 (cox-2), and P13K/Akt signaling and inhibited the phosphorylation of NF-κB and nuclear factor-kappa-B-inhibitor alpha (Iκ-Bα) in DMBA-induced hamsters. Conclusions The oral administration of lycorine effectively inhibited tumor cell proliferation, restored the antioxidant, LPO, and detoxification enzymes, and inhibited NF-κB signaling in oral tumorigenesis. Thus, the use of lycorine after a proper clinical trial could be effective for oral tumorigenesis treatment.