Black tea induces tumor cell apoptosis by Bax translocation, loss in mitochondrial transmembrane potential, cytochrome c release and caspase activation.
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 IC50 at 100 microg/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.
Bhattacharyya
Arindam
A
Bose Institute, P-1/12 CIT Scheme VII M, Kolkata, India.
Lahiry
Lakshmishri
L
Mandal
Debaprasad
D
Sa
Gaurisankar
G
Das
Tanya
T
D000818:Animals; D016588:Anticarcinogenic Agents; D017209:Apoptosis / Q000502:physiology*; D002286:Carcinoma, Ehrlich Tumor; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000032:analysis; D007425:Intracellular Membranes / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000502:physiology; D021381:Protein Transport; D013662:Tea
D016588:Anticarcinogenic Agents; D013662:Tea; D045304:Cytochromes c