(-)-Epigallocatechin-3-gallate (EGCG) increases the viability of serum-starved A549 cells through its effect on Akt.
The effect of epigallocatechin gallate (EGCG) on cell survival was studied by using serum-starved A549 non-small cell lung carcinoma (NSCLC) cells. A MTT assay showed that EGCG significantly increased the viability of serum-starved A549 cells compared to the control cells, though EGCG at high concentration (approximately 300 microM) had no protective effect against serum withdrawal-induced cell apoptosis. Western blots showed increased immunoreactivity for phospho-Akt and phospho-GSK3beta in EGCG-treated cells. To determine the mechanism for Akt phosphorylation, cells were pretreated with various kinase inhibitors before exposure to EGCG. Only LY294002 inhibited Akt activation induced by EGCG, implying that EGCG-induced Akt activation is PI3K dependent. Both phospho-Raf-1 and Raf-1 proteins were significantly decreased, whereas B-raf expression was not altered. This suggests that the Raf kinases have no role in the increased cell survival caused by EGCG. This study has shown that EGCG protects A549 cells from apoptosis induced by serum deprivation via Akt activation and this protective effect may limit the clinical use of EGCG in treating and preventing NSCLC.
Kim
Myung Jin
MJ
Department of Oral Pathology, Pusan National University, Yang San, South Korea.
Kim
Hyung Il
HI
Chung
Jin
J
Jeong
Tae Sung
TS
Park
Hae Ryoun
HR
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D013997:Time Factors
C486377:AKTIP protein, human; D048868:Adaptor Proteins, Signal Transducing; D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D016895:Culture Media, Serum-Free; D002392:Catechin; C045651:epigallocatechin gallate; D019869:Phosphatidylinositol 3-Kinases; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D019908:Proto-Oncogene Proteins c-raf; D038362:Glycogen Synthase Kinase 3