Abrogation of HDGF by EGCG enhances cisplatin-induced apoptosis and sensitizes A549 cells to chemotherapy. - GreenMedInfo Summary

PURPOSE: To search for regulated proteins in response to green tea (-)-epigallocatechin-3-gallate (EGCG) in A549 lung cancer cells.

EXPERIMENTAL DESIGN: Two-dimensional electrophoresis and electrospray ionization/multi-stage mass spectrometry (ESI-MS/MS) was performed to identify modulated proteins in A549 cells treated with EGCG. Cell migration was evaluated by transwell assays. RNA interference was used to silence the hepatoma-derived growth factor (HDGF). Caspase-3, caspase-9, and HDGF were immunodetected by Western blot assays. Flow cytometry was used for detection of mitochondrial membrane potential and apoptosis.

RESULTS: We found that HDGF expression was three-fold suppressed by EGCG treatment. Down-regulation of HDGF by EGCG was confirmed using anti-HDGF antibodies in three lung cancer cell lines. EGCG treatment and HDGF abrogation by RNA interference resulted in a decreased migration of A549 cells. In addition, EGCG induced a marked synergistic effect with cisplatin in cell death. Consistently, an enhanced cytotoxicity in HDGF-silenced cells was also found. Cell death was associated to increased apoptosis, disruption of the mitochondrial membrane potential, and activation of caspase-3 and caspase-9.

CONCLUSION AND CLINICAL RELEVANCE: Our data suggest for the first time that abrogation of HDGF by EGCG enhances cisplatin-induced apoptosis and sensitize A549 cells to chemotherapy. Therefore, we propose that decreasing the HDGF levels by using EGCG may represent a novel strategy in lung cancer therapy. This article is protected by copyright. All rights reserved.