Tea polyphenols can restrict benzo[a]pyrene-induced lung carcinogenesis by altered expression of p53-associated genes and H-ras, c-myc and cyclin D1.
The modulatory influence of tea polyphenols (epigallocatechin gallate, epicatechin gallate and theaflavin) on benzo[a]pyrene (B[a]P)-induced lung carcinogenesis in mice was analyzed using histopathological and molecular parameters. Progression of lung lesions was restricted at the hyperplastic stage by tea polyphenols. A significant reduction in cellular proliferative index and an increase in apoptotic index were noted in the restricted lung lesions. High expression of H-ras, c-myc, cyclin D1 and p53 genes was seen at the inflammatory stage (9th week) and in subsequent premalignant lesions, but down-regulation of H-ras at the hyperplastic stage (17th week). Expression of bcl-2 was high in hyperplastic lesions, whereas the expression of mdm2 and bcl-xl increased only at the moderately dysplastic stage (36th week). The tea polyphenols inhibited inflammatory response in the lung lesions on the 9th week, when decreased expression of H-ras and c-myc and increased expression of bax were noted. Prolonged treatment (>9th week) with tea polyphenols resulted in changes in the expression of some additional genes, such as reduced expression of cyclin D1 (from the 17th week), bcl-2 (from the 26th week; mild dysplasia) and p21 (on the 36th week), and high expression of p53 (from the 17th week) and p27 (on the 36th week). These observations indicate that the tea polyphenols can restrict B[a]P-induced lung carcinogenesis by differential modulation of the expression of p53 and its associated genes such as bax, bcl-2, mdm2, p21 and p27, along with H-ras, c-myc and cyclin D1, at different time points.
Manna
Sugata
S
Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata 700026, India.
Mukherjee
Sudeshna
S
Roy
Anup
A
Das
Sukta
S
Panda
Chinmay Kr
CK
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001564:Benzo(a)pyrene; D044946:Biflavonoids / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D019938:Cyclin D1 / Q000096:biosynthesis*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D051379:Mice; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D013662:Tea; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D018631:ras Proteins / Q000096:biosynthesis*
D044946:Biflavonoids; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D016271:Proto-Oncogene Proteins c-myc; D013662:Tea; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; C056068:theaflavin; D001564:Benzo(a)pyrene; D002392:Catechin; C062669:epicatechin gallate; C045651:epigallocatechin gallate; D018631:ras Proteins