(-)-Epigallocatechin-3-gallate plays an antagonistic role in the antitumor effect of bortezomib in myeloma cells via activating Wnt/β-catenin signaling pathway.

Background: (-)-Epigallocatechin-3-gallate (EGCG) is an active constituent of green tea, whose efficacy on chemoprevention and chemotherapy has been extensively researched. Its anticancer potency with low toxicity and easy administration allows for its widespread use. Bortezomib, a proteasome inhibitor, has a significant influence on multiple myeloma (MM) in chemotherapy. Previous studies about the role of EGCG in the antitumor effect induced by bortezomib remain controversial.

Objectives: In our study, the effect of EGCG on the antitumor activity of bortezomib was investigated in myeloma cell lines U266 and RPMI8226, and the underlying mechanism was explored.

Material And Methods: The effect of EGCG on the antiproliferative and pro-apoptotic activities of bortezomib were investigated in myeloma cells using MTT assay and cell cycle analysis, respectively. The Wnt/β-catenin signaling pathway and related proteins were involved in this antagonistic effect and measured with western blot assay.

Results: Our results showed the inhibitory activity of EGCG on myeloma cells in a timeand dose-dependent manner. The EGCG neutralized the antiproliferative and pro-apoptotic effect induced by bortezomib by activating Wnt/β-catenin signaling pathway with the accumulation of β-catenin. An increase of the downstream target proteins as c-Myc and cyclin D1 was also observed. was also observed. These findings demonstrated the antagonistic role of EGCG in the antitumor effect of bortezomib likely through the activated Wnt/β-catenin signaling pathway and the upregulated target proteins.

Conclusions: When bortezomib is involved in the MM chemotherapy, the consumption of green tea should be avoided in order to maintain the biological efficacy of bortezomib.