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.
Ganguly
Chaiti
C
Dept. of Cancer Chemoprevention, Chittarajan National Cancer Institute, 37 S.P. Mukherjee Road, Kolkata 700026, India.
Saha
Prosenjit
P
Panda
Chinmay Kr
CK
Das
Sukta
S
D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D005419:Flavonoids / Q000494:pharmacology*; D019254:Genes, bcl-2; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms / Q000473:pathology*; D009362:Neoplasm Metastasis; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D013662:Tea; D014407:Tumor Cells, Cultured
D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D013662:Tea