Modulating effect of hesperetin on the molecular expression pattern of apoptotic and cell proliferative markers in 7,12-dimethylbenz(a)anthracene-induced oral carcinogenesis

Arch Physiol Biochem. 2020 Dec;126(5):430-439. doi: 10.1080/13813455.2018.1555600. Epub 2019 Jan 20.

Abstract

Oral squamous cell carcinoma (OSCC) is widespread malignant neoplasm and refractory cancers in worldwide. Here, we studied the chemopreventive potential of hesperetin on 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch carcinogenesis (HBPCs). Oral tumours were developed in the buccal pouches of male golden Syrian hamsters by topical application of 0.5% DMBA three times a week for 10 weeks. This causes sequentially hyperplasia, dysplasia and well differentiates squamous cell carcinoma (SCC) with up-regulation of molecular markers like mutant-p53, Caspase-3 and caspase-9 and cyclin-D1. Histology, immunohistochemistry (IHC), real time PCR (qRT-PCR) and western blot analysis of hesperetin treated animals shows a reversal in the above expression pattern to near normal in buccal mucosal tissue. Therefore, hesperetin exhibits the potential protective effect against DMBA-induced oral cancer through apoptotic and anti-proliferative properties. However, a long-term observation would be needed to confirm the possibility of malignant change of the resulted dysplastic lesions upon hesperetin pretreatment.

Keywords: DMBA; Oral cancer; apoptotic; cell proliferative; hesperetin.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / toxicity*
  • Animals
  • Apoptosis*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinogens / toxicity
  • Cell Proliferation*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Hesperidin / pharmacology*
  • Male
  • Mesocricetus
  • Mouth Neoplasms / chemically induced
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology
  • Protective Agents / pharmacology

Substances

  • Biomarkers, Tumor
  • Carcinogens
  • Protective Agents
  • 9,10-Dimethyl-1,2-benzanthracene
  • Hesperidin
  • hesperetin