Literature DB >> 26175166

Differential proteomic analysis reveals that EGCG inhibits HDGF and activates apoptosis to increase the sensitivity of non-small cells lung cancer to chemotherapy.

Ali Flores-Pérez1, Laurence A Marchat2,3, Lidia López Sánchez1, Diana Romero-Zamora1, Elena Arechaga-Ocampo4, Nayeli Ramírez-Torres1, José Díaz Chávez5, Ángeles Carlos-Reyes6, Horacio Astudillo-de la Vega7, Erika Ruiz-García8, Abrahan González-Pérez1, César López-Camarillo1.   

Abstract

PURPOSE: To search for regulated proteins in response to green tea (-)-epigallocatechin-3-gallate (EGCG) in A549 lung cancer cells. EXPERIMENTAL
DESIGN: 2DE and ESI/multistage MS (ESI-MS/MS) were 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 threefold suppressed by EGCG treatment. Downregulation 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.
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Entities:  

Keywords:  Apoptosis; EGCG; HDGF; Lung cancer; Migration; Therapy

Mesh:

Substances:

Year:  2015        PMID: 26175166     DOI: 10.1002/prca.201500008

Source DB:  PubMed          Journal:  Proteomics Clin Appl        ISSN: 1862-8346            Impact factor:   3.494


  9 in total

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