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 m ixture (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 gro wth, apoptosis, and gene expression in normal and cancerous cells. We showe d that TF-2 (10-50 muM) 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 IC(50)s of TF-2 for the growth inh ibition of WI38 and WI38VA cells were, respectively, 300 and 3 muM. The oth er two black tea polyphenols, TF-I and TF-3, did not exhibit such different ial 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-in hibitory effect of TF-2. Cox-2 has been implicated in intestinal carcinogen esis. Among the tea polyphenols tested, TF-2 and, to a lesser degree, (-)-e pigallocatechin gallate inhibited cyclooxygenase (Cox)-2 gene expression. T F-2 at 50 muM completely blocked the serum-induced Cox-2 gene expression at both mRNA and protein level. Other genes, including c-fos, c-myc, thymidin e kinase, proliferating cell nuclear antigen, BRCA1, BRCA2, and Cox-1, were not significantly affected by TF-2. These findings suggest that TF-2 may b e responsible, at least in part, for the chemopreventive activity in black tea extracts.