Induction of apoptosis and cell cycle arrest in cancer cells by in vivo metabolites of teas.
Nutr Cancer 2000;38(2):265-73
Zhang G; Miura Y; Yagasaki K
Department of Applied Biological Science, Tokyo Noko University, Japan.
The present study was conducted to determine in vivo possibilities of inducing apoptosis and cell cycle arrest in rat cancer cells by green, oolong, and black teas and also to further identify the mechanisms inhibiting cancer cell proliferation by the sera from tea-treated rats. The tea extracts from these three kinds of tea, the rat sera obtained after oral intubation of the tea extracts, and the tea polyphenolic compounds, (-)-epigallocatechin-3-gallate, (-)-epigallocatechin, (-)-epicatechin-3-gallate, and the aflavins, were used in the related tests. The extracts, the sera from the treated rats, and the polyphenolic compounds significantly inhibited the proliferation of a rat hepatoma cell line (AH109A) and murine B16 melanoma cells but not normal rat mesothelial (M) cells. (-)-Epicatechin exhibited synergistic effects with (-)-epigallocatechin-3-gallate, (-)-epicatechin-3-gallate, and theaflavins against AH109A cell proliferation. The fluorescence staining of the nuclei, electrophoresis detection of DNA fragmentation, and analysis of cell cycle indicated that the sera from the tea-treated rats, the tea extracts, and the related tea components resulted in loss of viability, apoptosis, and cell cycle arrest at the G1 phase in AH109A and/or B16 cells, but not in normal M cells. Our results suggest that induction of apoptosis and cell cycle arrest may be important mechanisms of in vivo proliferation inhibition of AH109A and other cancer cells by these teas.