(-)-Epigallocatechin (EGC) of green tea induces apoptosis of human breast cancer cells but not of their normal counterparts.
(-)-Epigallocatechin (EGC), one of green tea polyphenols, has been shown to inhibit growth of cancer cells. However its mechanism of action is poorly known. We show here that EGC strongly inhibited the growth of breast cancer cell lines (MCF-7 and MDA-MB-231) but not that of normal breast epithelial cells. The inhibition of breast cancer cell growth was due to an induction of apoptosis, without any change in cell cycle progression. MCF-7 cells are known to express a wild-type p53 whereas MDA-MB-231 cells express a mutated p53. The fact that EGC induced apoptosis in both these cell lines suggests that the EGC-triggered apoptosis is independent of p53 status. Moreover, neutralizing antibodies against the death receptor Fas and inhibitors of caspases, such as caspase-8 and -10, efficiently inhibited the EGC-triggered apoptosis. In addition, immunoblotting revealed that EGC treatment was correlated with a decrease in Bcl-2 and an increase in Bax level. These results suggest that EGC-triggered apoptosis in breast cancer cells requires Fas signaling.
Vergote
David
D
Laboratoire de Biologic du Développement (UPRES-EA 1033), Université des Sciences et Technologies de Lille, Villeneuve d'Ascq, France.
Cren-Olivé
Cécile
C
Chopin
Valérie
V
Toillon
Robert-Alain
RA
Rolando
Christian
C
Hondermarck
Hubert
H
Le Bourhis
Xuefen
X
D017209:Apoptosis / Q000187:drug effects*; D001940:Breast / Q000166:cytology / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D019938:Cyclin D1 / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D064429:Fatty Acid Synthases / Q000378:metabolism; D005260:Female; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019938:Cyclin D1; D002392:Catechin; D064429:Fatty Acid Synthases; D020169:Caspases; C057580:gallocatechol