Black tea induces tumor cell apoptosis by Bax translocation, loss in mitochondrial transmembrane potential, cytochrome c release and caspase activation

Abstract

Recently the anti-cancer role of black tea has gained immense importance. Nevertheless, the signaling pathways underlying black tea-induced tumor cell death are still unknown. Previously we reported that black tea induces Ehrlich's ascites carcinoma (EAC) cell apoptosis by changing the balance between pro-and anti-apoptotic proteins. It is now well accepted that many cell death pathways converge at the mitochondria to decrease mitochondrial transmembrane potential (MTP) thereby releasing apoptogenic proteins and resulting in the activation of effecter caspases responsible for the biochemical and morphological alterations associated with apoptosis. The role of pro-apoptotic protein, Bax, in initiating mitochondrial death cascade has also been established. Here we demonstrate that in culture black tea extract induces EAC apoptosis in a dose-dependent manner -with IC 50 at 100 lg/ml. At this dose, intracellular Bax level increases in EAC followed by its translocation from cytosol to mitochondria resulting in loss in MTP. A search for the downstream pathway further reveals that black tea induces mitochondrial cytochrome c release and activates caspases 9 and 3 by 2 pathways, a) independent of and b) dependent on MTP loss. Interestingly, Black tea-induced death signal might probably be amplified through mitochondrial membrane depolarization via a feedback activation loop from caspase 3. All these findings indicate that black tea initiates mitochondrial death cascade in EAC cells and thereby results in EAC apoptosis. ' 2005 Wiley-Liss, Inc.

In vitro evaluation of the anticancer effect of lactoferrin and tea polyphenol combination on oral carcinoma cells

“…The decrease in Bcl-2/Bax ratio observed in the present study can lead to a decrease in Dj m with subsequent activation of caspase-3 activity probably via the cytochrome c/Apaf-1/caspase-9 pathway. These findings are consistent with previous reports on the apoptosis inducing effects of tea polyphenols on various cancer cell lines (Bhattacharyya et al, 2005;Kundu et al, 2005;Nakazato et al, 2005a,b;Qanungo et al, 2005). In a recent report, we have demonstrated that combined administration of tea polyphenols and bLF inhibits hamster buccal pouch carcinogenesis by inducing apoptosis through decreasing Bcl-2/Bax ratio and increasing caspase-3 expression (Chandra Mohan et al, 2006).…”

“…Tea polyphenols are known to mediate their anticancer properties by induction of apoptosis (Bhattacharyya et al, 2005;Kundu et al, 2005;Nakazato et al, 2005a,b;Qanungo et al, 2005). The present results also demonstrate that green and black tea polyphenols inhibit the growth of CAL-27 cells by inducing apoptosis as revealed by characteristic changes in nuclear morphology and A o peak.…”

Regulation of cell growth through cell cycle arrest and apoptosis in HPV 16 positive human cervical cancer cells by tea polyphenols

“…2) which showed that GTP has potential to regulate the transition of cells from G2 to M phase by down modulation of nuclear factor-kappaB [26]. Tea polyphenols are known to mediate their anti-cancer properties by induction of apoptosis [27,28]. The present study also supports the same notions as revealed by characteristic increase in cells in sub G1 peak of cell cycle and annexin-V and PI staining (Figs.…”

Berbamine induces apoptosis in human hepatoma cell line SMMC7721 by loss in mitochondrial transmembrane potential and caspase activation

“…Activation of apoptotic pathway is a key mechanism by which cytotoxic drugs kill cancer cells. Black tea, tanshinone IIA and other natural products inhibit tumor growth (Bhattacharyya et al, 2005: Wang et al, 2005Hsu et al, 2005). Nucleus condensation and apoptotic bodies appearance are universal characteristics of cells undergoing apoptosis.…”