Inhibition of growth, induction of apoptosis and alteration of gene expression by tea polyphenols in the highly metastatic human lung cancer cell line NCI-H460.

Lung cancer is a complex group of diseases but each lesion is thought to originate from a single mutated progenitor cell. It is evident that multiple genetic changes are involved in the generation of each specific type of lung cancer. Due to the high complexity of these processes and rapid metastasis, treatment of advanced lung cancer, particularly of NSCLCs, is far from satisfactory. Thus, there is a need for innovative strategies for modulation of adverse alteration in protooncogene or tumor suppressor genes so that lung carcinogenesis can be suppressed or delayed. To this end, we have evaluated the effects of tea compounds (theaflavins, epicatechin-gallate and epigallo-catechin-gallate) on proliferation and apoptosis and associated gene expression in a highly metastatic human lung cancer cell line NCI-H460. Significant reduction of cell proliferation, detected in situ by BrdU incorporation, and induction of apoptosis, assessed by the by the TUNEL method, were noted following treatments. Expression of p53, Bcl-2, c-Myc and H-Ras, was localized by immunocytochemistry and analysed by Western blotting. Tea compounds upregulated expression of p53, downregulated expression of Bcl-2 but there was no significant influence on H-ras and c-Myc expressions. It is suggested that tea compounds can influence genetic alteration to disfavour, growth and survival of lung cancer cells.

The models for assessment of chemopreventive agents: single organ models.

Research in cancer chemoprevention involves a number of activities, the first and foremost of which is acquisition of detailed knowledge concerning the process of carcinogenesis and identification of points of intervention whereby the process can be reversed or stalled. Parallel to this is the search for ideal chemopreventive agents--natural or synthetic--and screening for their activity and efficacy in vitro and in vivo. For ethical reasons it is not possible to test new agents on humans, so preclinical studies are dependent on results first being obtained with suitable animal models. Since it is not possible for a single model to reflect the diversity and heterogeneity of human cancers, it is necessary to have as many different models as possible, depending on the requirement of the studies on different aspects of cancer biology. Advances in research on carcinogenesis and chemoprevention therefore have to be accompanied by development of appropriate laboratory animal models using a variety of carcinogens that produce tumours at different sites. Animal models have contributed significantly to our understanding of carcinogenesis and ways to intervene in the underlying processes. Many animal carcinogenesis and tumour models have been found to mirror corresponding human cancers with respect to cell of origin, morphogenesis, phenotype markers and genetic alteration. In spite of the fact that interpolation of data from animal studies to humans is difficult for various reasons, animal models are widely used for assessment of new compounds with cancer chemopreventive potential and for preclinical trials. So despite the movements of animal rights activists, animal models will continue to be used for biomedical research for saving human lives. In doing so, care should be taken to treat and handle the animals with minimal discomfort to them and ensuring that alternatives are used whenever possible.