Sodium orthovanadate potentiates EGCG-induced apoptosis that is dependent on the ERK pathway

Yun-Jung ChoiSung-Yup LimJu-Hyung WooYoung-Ho KimYoung Kyu KwonSeong-Il SuhSung-Hee LeeWha-Youl ChoiJong-Guk KimIn-Seon LeeJong-Wook ParkTaeg Kyu Kwon
Dept. of Immunology (면역학); Dept. of Microbiology (미생물학)
Issue Date
Biochemical and Biophysical Research Communications, Vol.305(1) : 176-185, 2003
Epigallocatechin-3-gallate (EGCG) is a potent chemopreventive agent in many test systems and has been shown to inhibit tumor promotion and induce apoptosis. In the present study, we determined the effect of vanadate, a potent inhibitor of tyrosine phosphatase, on EGCG-induced apoptosis. Investigation of the mechanism of EGCG or vanadate-induced apoptosis revealed induction of caspase 3 activity and cleavage of phospholipase-γ1 (PLC-γ1). Furthermore, vanadate potentiated EGCG-induced apoptosis by mitogen-activated protein kinase (MAPK) signaling pathway. Treatment with EGCG plus vanadate for 24 h produced morphological features of apoptosis and DNA fragmentation in U937 cells. This was associated with cytochrome c release, caspase 3 activation, and PLC-γ1 degradation. EGCG plus vanadate activates multiple signal transduction pathways involved in coordinating cellular responses to stress. We demonstrate a requirement for extracellular signal-regulated protein kinase (ERK), a member of the mitogen-activated protein kinase family in EGCG plus vanadate-induced apoptosis in U937 cells. Elevated ERK activity that contributed to apoptosis by EGCG plus vanadate was supported by PD98059 and U0126, chemical inhibitor of MEK/ERK signaling pathway, prevented apoptosis. Taken together, our finding suggests that ERK activation plays an active role in mediating EGCG plus vanadate-induced apoptosis of U937 cells and functions upstream of caspase activation to initiate the apoptotic signal. Keywords EGCG; Vanadate; U937 cells; Apoptosis; Caspase 3; ERK
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1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Microbiology (미생물학)
Keimyung Author(s)
박종욱; 권택규; 서성일
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