Bioactivity-guided fractionation and identification of active black tea components for inhibition of prostate cancer cell growth and angiogenesis.

B228

Until recently, tea research has been centered around green tea, primarily because of its high content of tea catechins such as epigallocatechin gallate (EGCG). It is believed that tea catechins are major active components in tea, and that the fermentation process used for black tea preparation reduces tea catechin levels, therefore black tea may be less active than green tea. Although it may be true that green tea is potent for prevention of certain diseases, black tea may have a unique chemical pattern and may be potent in prevention of other diseases. Our preliminary studies have consistently demonstrated that black tea may be more potent than green tea in prostate cancer prevention in several clinically relevant animal models of prostate tumors as well as in cell culture studies. Further studies indicated that, although whole black tea had potent anti-prostate cancer activity, the black tea polyphenols fraction had much less activity. These preliminary data suggest that black tea may contain bioactive components, other than tea polyphenols, to contribute to the potent anti-prostate cancer activity of black tea. The objective of the current studies was to apply cellular activity-based bioassays to guide fractionation and identification of active black tea components. Black tea was extracted and initially fractionated via column chromatography into seven fractions. The bioactivities of these fractions in inhibiting the growth and invasion of prostate cancer cells and in inhibiting the in vitro angiogenesis as measured by the growth, migration and tube formation of endothelial cells. The chemical profiles of these fractions were determined by RP-HPLC. We found that the fraction 2 (F2) had the most potent anti-angiogenesis activity in vitro with the IC₅₀ around 25μg/ml, but it had limited anti-prostate cancer activity. We further fractionated F2 into three sub-fractions (F2-1, 2, and 3). The in vitro assays showed the F2-3 subfraction retained the most of anti-angiogenesis activity of the F2, with the IC₅₀ around 8μg/ml. We also found that the fraction 3 and the fraction 4 of black tea extract had the most potent activity in inhibiting the growth of prostate cancer cells. We are in process to further identify the active subfraction(s) for prostate cancer growth inhibition, and to determine the underlying molecular mechanisms by which the F2-3 inhibits angiogenesis.