Differential effects of theaflavin monogallates on cell growth, apoptosis, and Cox-2 gene expression in cancerous versus normal cells.
Theaflavin (TF-1), theaflavin-3-monogallate and theaflavin-3'-monogallate mixture (TF-2), and theaflavin-3,3'-digallate (TF-3) are the major black tea polyphenols. Here we compared the effects of these polyphenols on cell growth, apoptosis, and gene expression in normal and cancerous cells. We showed that TF-2 (10-50 microM) inhibited the growth of SV40 transformed WI38 human cells (WI38VA) and Caco-2 colon cancer cells but had little effect on the growth of their normal counterparts. The IC50s of TF-2 for the growth inhibition of WI38 and WI38VA cells were, respectively, 300 and 3 microM. The other two black tea polyphenols, TF-1 and TF-3, did not exhibit such differential growth-inhibitory effect. TF-2, but not TF-1 or TF-3, induced apoptosis in transformed WI38VA cells but not in normal WI38 cells, suggesting that apoptosis was responsible, at least in part, for the differential growth-inhibitory effect of TF-2. Cox-2 has been implicated in intestinal carcinogenesis. Among the tea polyphenols tested, TF-2 and, to a lesser degree, (-)-epigallocatechin gallate inhibited cyclooxygenase (Cox)-2 gene expression. TF-2 at 50 microM completely blocked the serum-induced Cox-2 gene expression at both mRNA and protein level. Other genes, including c-fos, c-myc, thymidine kinase, proliferating cell nuclear antigen, BRCA1, BRCA2, and Cox-1, were not significantly affected by TF-2. These findings suggest that TF-2 may be responsible, at least in part, for the chemopreventive activity in black tea extracts.
Lu
J
J
Department of Chemistry, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854-8087, USA.
Ho
C T
CT
Ghai
G
G
Chen
K Y
KY
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D044946:Biflavonoids; D018938:Caco-2 Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D002392:Catechin; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002461:Cell Line, Transformed; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D046508:Culture Techniques; D051546:Cyclooxygenase 2; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics; D013662:Tea
D000975:Antioxidants; D044946:Biflavonoids; D006131:Growth Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D013662:Tea; C088983:theaflavine gallate; C077197:theaflavin digallate; D005707:Gallic Acid; D002392:Catechin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases