Black tea extract can modulate protein expression of H-ras, c-Myc, p53, and Bcl-2 genes during pulmonary hyperplasia, dysplasia, and carcinoma in situ

J Environ Pathol Toxicol Oncol. 2005;24(3):211-24. doi: 10.1615/jenvpathtoxoncol.v24.i3.70.

Abstract

Lung cancer has emerged as one of the leading causes of cancer death in most developed and many developing countries of the world. In the absence of effective screening and early detection methods of lung cancer and overall poor prognosis, the 5-year survival following treatment has not improved significantly over the last two decades. It is hoped that the risk of the disease can be minimized by preventive measures. One aspect of lung cancer prevention emphasizes the cessation of tobacco smoking, and another strategy envisages reversal or restriction of the process of lung carcinogenesis by chemopreventive intervention. The latter strategy, however, demands a deeper understanding of the pathogenesis of the disease and the identification of the ideal point of intervention. In the present investigation, we assessed the role of the antioxidant tea components theaflavins (TF) and epigallocatechin gallate (EGCG) for their chemopreventive potential and molecular mechanism of action when administered at the post-initiation phase of lung carcinogenesis in an experimental mouse model. We serially examined the histopathological changes in the lung of mice administered benzo(a)pyrene and correlated them with the frequency of proliferative and apoptotic cells in situ as well as with the expression of H-ras, c-Myc, p53, and Bcl-2 genes, which play key roles in the histopathogenesis of neoplasia. Our findings indicate that both TF and EGCG can influence gene expression to modulate the process of carcinogenesis through the regulation of apoptosis. This results in a lowered incidence and delayed onset of preinvasive lung lesions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Anticarcinogenic Agents / therapeutic use
  • Apoptosis / drug effects
  • Benzo(a)pyrene / toxicity
  • Biflavonoids / therapeutic use
  • Carcinoma in Situ / genetics
  • Carcinoma in Situ / metabolism*
  • Carcinoma in Situ / pathology
  • Catechin / analogs & derivatives
  • Catechin / therapeutic use
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Hyperplasia
  • Lung / drug effects
  • Lung / metabolism*
  • Lung / pathology
  • Lung Neoplasms / prevention & control*
  • Male
  • Mice
  • Plant Extracts / therapeutic use
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogenes*
  • Tea* / chemistry

Substances

  • Anticarcinogenic Agents
  • Biflavonoids
  • Plant Extracts
  • Proto-Oncogene Proteins
  • Tea
  • theaflavin
  • Benzo(a)pyrene
  • Catechin
  • epigallocatechin gallate