Differential proteomic analysis reveals that EGCG inhibits HDGF and activates apoptosis to increase the sensitivity of non-small cells lung cancer to chemotherapy
| Autor: | Lidia López Sánchez, Ángeles Carlos-Reyes, Laurence A. Marchat, Ali Flores-Pérez, José Díaz Chávez, Horacio Astudillo-de la Vega, Diana Romero-Zamora, Erika Ruiz-García, César López-Camarillo, Elena Aréchaga-Ocampo, Nayeli Ramírez-Torres, Abrahan González-Pérez |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Proteomics Programmed cell death Lung Neoplasms Cell Survival Clinical Biochemistry Apoptosis Biology complex mixtures Catechin Flow cytometry 03 medical and health sciences Structure-Activity Relationship 0302 clinical medicine Downregulation and upregulation Carcinoma Non-Small-Cell Lung Antineoplastic Combined Chemotherapy Protocols medicine Tumor Cells Cultured Humans Cell Proliferation A549 cell Cisplatin medicine.diagnostic_test Dose-Response Relationship Drug Cell growth food and beverages Cell migration Molecular biology 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Intercellular Signaling Peptides and Proteins Drug Screening Assays Antitumor medicine.drug |
| Zdroj: | Proteomics. Clinical applications. 10(2) |
| ISSN: | 1862-8354 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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