Histological and immunohistochemical evaluation of the chemopreventive role of lycopene in tongue carcinogenesis induced by 4-nitroquinoline-1-oxide

Arch Oral Biol. 2011 Jul;56(7):664-71. doi: 10.1016/j.archoralbio.2010.12.007. Epub 2011 Jan 8.


Objective: Increasing attention has been given to the potential protective roles of specific antioxidant nutrients found in fruits and vegetables. However, there are relatively few reports on the cancer chemopreventive effects of lycopene or tomato carotenoids in animal models. Therefore, the chemopreventive efficacy of lycopene with regard to oral carcinogenesis was investigated using 4-nitroquinoline-1-oxide (4-NQO) induced tongue squamous cell carcinoma.

Materials and methods: Twenty albino rats were equally divided into 2 groups. 4-NQO was dissolved in the drinking water (20 ppm) for rats of both groups. Rats in group 2 were administered lycopene at a dose of 2.5mg/kg body weight by intragastric intubation once a day. Incidence of oral neoplasms and histopathological changes were microscopically evaluated after 32 weeks of administration of the specific treatments. Moreover, immunohistochemical expressions of proliferating cell nuclear antigen (PCNA), E-cadherin and β-catenin were analysed in tongue specimens using an image analyser computer system.

Results: Lycopene treatment significantly decreased the incidence of 4-NQO induced tongue carcinogenesis. A decreased percentage of PCNA-positive nuclei was associated with lycopene treatment. Proliferating cells were mainly confined to the basal and parabasal epithelial cell layers. Increased E-cadherin and β-catenin immunoexpression was recorded in the lycopene treated group in comparison to the carcinogen group.

Conclusion: Results of the present study indicate that lycopene can exert protective effects against 4-NQO induced tongue carcinogenesis through reduction in cell proliferation and enhanced cellular adhesion, suggesting a new mechanism for the anti-invasive effect of lycopene. Further studies are needed to provide more definitive answers to the question of the anticancer effects of lycopene.

Publication types

  • Comparative Study

MeSH terms

  • 4-Nitroquinoline-1-oxide / adverse effects*
  • Animals
  • Anticarcinogenic Agents / administration & dosage
  • Anticarcinogenic Agents / therapeutic use*
  • Antioxidants / administration & dosage
  • Antioxidants / therapeutic use*
  • Basement Membrane / drug effects
  • Basement Membrane / pathology
  • Cadherins / analysis
  • Carcinogens*
  • Carcinoma in Situ / chemically induced
  • Carcinoma in Situ / pathology
  • Carcinoma, Squamous Cell / chemically induced
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / prevention & control*
  • Carotenoids / therapeutic use*
  • Cell Nucleus / drug effects
  • Cell Nucleus / ultrastructure
  • Chemoprevention
  • Disease Models, Animal
  • Epithelial Cells / drug effects
  • Epithelial Cells / pathology
  • Hyperplasia
  • Image Processing, Computer-Assisted / methods
  • Immunohistochemistry
  • Intubation, Gastrointestinal
  • Lycopene
  • Male
  • Proliferating Cell Nuclear Antigen / analysis
  • Random Allocation
  • Rats
  • Time Factors
  • Tongue / pathology
  • Tongue Neoplasms / chemically induced
  • Tongue Neoplasms / pathology
  • Tongue Neoplasms / prevention & control*
  • beta Catenin / analysis


  • Anticarcinogenic Agents
  • Antioxidants
  • Cadherins
  • Carcinogens
  • Proliferating Cell Nuclear Antigen
  • beta Catenin
  • Carotenoids
  • 4-Nitroquinoline-1-oxide
  • Lycopene