Schedule-Dependent Effect of Epigallocatechin-3-Gallate (EGCG) with Paclitaxel on H460 Cells

BACKGROUND: Epigallocatechin-3-gallate (EGCG), a major biologically active component of green tea, has anti-cancer activity in human and animal models. We investigated the schedule-dependent effect of EGCG and paclitaxel on growth of NCI-H460 non-small cell lung cancer cells. METHODS: To investigate the combined effect of EGCG (E) and paclitaxel (P), combination indices (CIs) were calculated, and cell cycle analysis was performed. For the effect on cell apoptosis, western blot analysis was also performed. RESULTS: CI analysis demonstrated that both concurrent and sequential E → P treatments had antagonistic effects (CIs >1.0), but sequential P → E had synergistic effects (CIs <1.0), on the growth inhibition of NCI-H460 cells. In the cell cycle analysis, although paclitaxel induced G(2)/M cell cycle arrest and increased the sub-G1 fraction, concurrent EGCG and paclitaxel treatments did not have any additive or synergistic effects compared with the paclitaxel treatment alone. However, western blot analysis demonstrated that sequential P → E treatment decreased the expression of Bcl-2 and procaspase-3 and increased poly(ADP-ribose) polymerase (PARP) cleavage; while minimal effects were seen with concurrent or sequential E → P treatments. CONCLUSION: Concurrent or sequential E → P treatment had opposite effects to P → E treatment, where P → E treatment showed a synergistic effect on growth inhibition of NCI-H460 cells by inducing apoptosis. Thus, the efficacy of EGCG and paclitaxel combination treatment seems to be schedule-dependent.