Usnic acid attenuates 7,12-dimethylbenz[a] anthracene (DMBA) induced oral carcinogenesis through inhibiting oxidative stress, inflammation, and cell proliferation in male golden Syrian hamster model

J Biochem Mol Toxicol. 2024 Jan;38(1):e23553. doi: 10.1002/jbt.23553. Epub 2023 Oct 16.

Abstract

In this study, we investigated the chemopreventive efficacy of usnic acid (UA), an effective secondary metabolite component of lichens, against 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral squamous cell carcinoma (OSCC) in the hamster model. Initially, the buccal pouch carcinogenesis was induced by administering 0.5% DMBA to the HBP (hamster buccal pouch) region about three times a week until the 10th week. Then, UA was orally treated with different concentrations (25, 50, 100 mg/kg b.wt) on alternative days of DMBA exposure, and the experimental process ended in the 16th week. After animal experimentation, we observed 100% tumor incidence with well-differentiated OSCC, dysplasia, and hyperplasia lesions in the DMBA-induced HBP region. Furthermore, the UA treatment of DMBA-induced hamster effectively inhibited tumor growth. In addition, UA upregulated antioxidant levels, interfered with the elevated lipid peroxidation by-product of thiobarbituric acid reactive substances, and changed the activities of the liver detoxification enzyme (Phase I and II) in DMBA-induced hamsters. Furthermore, immunohistochemical staining of inflammatory markers (iNOS and COX-2) and proliferative cell markers (cyclin-D1 and PCNA) were upregulated in the buccal pouch part of hamster animals induced with DMBA. Notably, the oral administration of UA significantly suppressed these markers during DMBA-induced hamsters. Collectively, our findings revealed that UA exhibits antioxidant, anti-inflammatory, antitumor, and apoptosis-inducing characteristics, demonstrating UA's protective properties against DMBA-induced HBP carcinogenesis.

Keywords: DMBA; OSCC; antioxidants; antitumor; usnic acid.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / toxicity
  • Animals
  • Anthracenes
  • Antioxidants / metabolism
  • Benzofurans*
  • Carcinogenesis / chemically induced
  • Carcinogens / toxicity
  • Carcinoma, Squamous Cell* / chemically induced
  • Cell Proliferation
  • Cricetinae
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Male
  • Mesocricetus
  • Mouth Neoplasms* / chemically induced
  • Mouth Neoplasms* / pathology
  • Mouth Neoplasms* / prevention & control
  • Oxidative Stress

Substances

  • usnic acid
  • Antioxidants
  • 9,10-Dimethyl-1,2-benzanthracene
  • Anthracenes
  • Carcinogens
  • Benzofurans