TY - JOUR
T1 - Differential proteomic analysis reveals that EGCG inhibits HDGF and activates apoptosis to increase the sensitivity of non-small cells lung cancer to chemotherapy
AU - Flores-Pérez, Ali
AU - Marchat, Laurence A.
AU - Sánchez, Lidia López
AU - Romero-Zamora, Diana
AU - Arechaga-Ocampo, Elena
AU - Ramírez-Torres, Nayeli
AU - Chávez, José Díaz
AU - Carlos-Reyes, Ángeles
AU - Astudillo-de la Vega, Horacio
AU - Ruiz-García, Erika
AU - González-Pérez, Abrahan
AU - López-Camarillo, César
N1 - Publisher Copyright:
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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.
AB - 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.
KW - Apoptosis
KW - EGCG
KW - HDGF
KW - Lung cancer
KW - Migration
KW - Therapy
UR - http://www.scopus.com/inward/record.url?scp=84956799636&partnerID=8YFLogxK
U2 - 10.1002/prca.201500008
DO - 10.1002/prca.201500008
M3 - Artículo
C2 - 26175166
SN - 1862-8346
VL - 10
SP - 172
EP - 182
JO - Proteomics - Clinical Applications
JF - Proteomics - Clinical Applications
IS - 2
ER -