Induction of apoptosis in human leukemia cells by black tea and its polyphenol theaflavin.
Treatment of human leukemic cell lines HL-60 and K-562 with extracts of green and black tea and their polyphenols epigallocatechin gallate and theaflavins, respectively, showed a dose dependent inhibition of growth as a result of cytotoxicity and suppression of cell proliferation. Based on the IC50 values obtained from cytotoxicity data it was clearly evident that black tea was as efficient as green tea. Analysis of polyphenol contents of tea extracts revealed that not only epigallocatechin gallate, which is a predominant polyphenol of green tea, but also theaflavin that is abundantly present in black tea affords significant chemotherapeutic action by imparting cytotoxicity to human leukemic cells. Electrophoretic analysis of fragmented DNA from treated cells displayed characteristic ladder pattern. Flow cytometric analysis revealed the dose dependent increase in sub-G1 peak. These criteria confirmed that cytotoxic activity of green and black tea was due to induction of apoptosis. Such induction was found to be mediated through activation of caspases 3 and 8, particularly caspase 3 and by altering apoptosis related genes as evident by down-regulation of Bcl-2 and up-regulation of Bax proteins.
Kundu
Trina
T
Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, 37 S.P. Mukherjee Road, Kolkata 700 026, India.
Dey
Subhabrata
S
Roy
Madhumita
M
Siddiqi
M
M
Bhattacharya
R K
RK
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D044946:Biflavonoids / Q000494:pharmacology*; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002392:Catechin / Q000494:pharmacology*; D015536:Down-Regulation; D005419:Flavonoids / Q000032:analysis / Q000494:pharmacology; D005434:Flow Cytometry; D019254:Genes, bcl-2; D018922:HL-60 Cells; D006801:Humans; D010636:Phenols / Q000032:analysis / Q000494:pharmacology; D059808:Polyphenols; D013662:Tea / Q000737:chemistry*; D051028:bcl-2-Associated X Protein
D000975:Antioxidants; D044946:Biflavonoids; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D013662:Tea; D051028:bcl-2-Associated X Protein; C056068:theaflavin; D002392:Catechin; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases