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

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.

Epigallocatechin gallate induced apoptosis in Sarcoma180 cells in vivo: Mediated by p53 pathway and inhibition in U1B, U4-U6 UsnRNAs expression

“…Our study in vitro using a human lung cancer cell line NCI-H460 has shown reduction of cell proliferation and induction of apoptosis [37]. Analysis of p53, bcl-2, c-myc and H-ras expression revealed up regulation of p53, down regulation of bcl-2 and no significant change on H-ras and c-myc expression by the tea compounds, which is different from the observation of our in vivo study [38] where down regulation of H-ras and c-myc was noted.…”

Theaflavin-3, 3′-digallate induces apoptosis and G2 cell cycle arrest through the Akt/MDM2/p53 pathway in cisplatin-resistant ovarian cancer A2780/CP70 cells

“…Another explanation is that normal cells are resistant to the tumor necrosis factor related apoptosis-inducing ligand (TRAIL) due to the high TRID levels, whereas tumor lines carrying TRAIL-receptors in most cases can not be protected ( 31 ). Theaflavins have been reported to target the Fas/caspase-8 pathway to induce apoptosis in human breast cancer cells, and influence Bcl-2 protein expression in an experimental lung cancer mouse model ( 32 , 33 ). In this study, treatment with TF3 significantly regulated the protein expression of Bcl-2 family proteins (Bax, Bad and Bcl-xL), DR5, FADD, caspase-8 and -9 ( Figs.…”

Dactylone Inhibits Epidermal Growth Factor–Induced Transformation and Phenotype Expression of Human Cancer Cells and Induces G1-S Arrest and Apoptosis

“…The significance of the decreased p53 nuclear factor-dependent transcriptional activation induced by dactylone was verified using nonparametric statistical method MannWhitney U test (computer program Statistica 6.0, StatSoft). The tumor-suppressor p53 protein plays a critical role in apoptosis and an increase of p53 protein production followed by apoptosis is a common characteristic effect of cancer-preventive agents such as resveratrol (25), black tea extract (26), and many others. However, in our case, we did not observe an increase in p53 protein levels, although apoptosis was induced by dactylone.…”