We have examined whether
epigallocatechin-3-gallate (EGCG), and extract of
green tea, in combination with
taxane (i.e.,
paclitaxel and
docetaxel), exerts a synergistic activity in blocking human prostate PC-3ML
tumor cell growth in vitro and in vivo. Growth assays in vitro revealed that the IC(50) values were ∼30 µM, ∼3 nM, and ∼6 nM, for EGCG,
paclitaxel and
docetaxel, respectively. Isobolograms generated from the data clearly indicated that EGCG in combination with
paclitaxel or
docetaxel had an additive effect in blocking
tumor cell growth. EGCG combined with
taxane also had an additive effect to increase the expression of apoptotic genes, (p53, p73, p21, and
caspase 3) and the percent apoptosis observed in vitro and in
tumor modeling studies in severe combined immunodeficient mice. The
tumor modeling studies clearly showed that EGCG plus
taxane injected intraperitoneally (i.p.) induced a significant increase in apoptosis rates (TUNEL assays) and eliminated preexisting
tumors generated from PC-3ML cells implanted i.p., increasing disease-free survival rates to greater than 90%. More importantly, the combination
therapy (i.p. biweekly) blocked
metastases after
intravenous injection of PC-3ML cells through the tail vein. In mice treated with EGCG plus
taxane, the disease-free survival rates increased from 0% (in untreated mice) to more than 70% to 80% in treated mice. Taken together, these data demonstrate for the first time that EGCG in combination with
taxane may provide a novel therapeutic treatment of advanced
prostate cancer.