Epigallocatechin-3-O-gallate induces acid sphingomyelinase activation through activation of phospholipase C

被引:9
作者
Bae, Jaehoon [1 ]
Kumazoe, Motofumi [1 ]
Takeuchi, Chieri [1 ]
Hidaka, Shiori [1 ]
Fujimura, Yoshinori [1 ]
Tachibana, Hirofumi [1 ]
机构
[1] Kyushu Univ, Fac Agr, Dept Biosci & Biotechnol, Div Appl Biol Chem, Fukuoka 8190395, Japan
关键词
EGCG; Cyclic guanosine monophosphate; Phospholipase C; Protein kinase C delta; Cancer; GREEN TEA POLYPHENOL; 67-KDA LAMININ RECEPTOR; BINDING PROTEIN; UP-REGULATION; EXPRESSION; CANCER; CELLS; DELTA; CGMP; EGCG;
D O I
10.1016/j.bbrc.2019.09.102
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Epigallocatechin-3-O-gallate (EGCG)-induced cyclic guanosine monophosphate (cGMP) plays a crucial role in EGCG-induced cell death in various types of cancer cells. However, little is known regarding the early molecular events after cGMP induction. In this study, we showed that cGMP induction is sufficient to induce the phosphorylation of protein kinase C delta (PKC delta) at Ser664, the crucial kinase for EGCG-induced activation of acid sphingomyelinase (ASM). Using a chemical inhibitor library, we revealed that the inhibitors of the negative regulators of diacylglycerol strongly increase the effect of EGCG. We also showed that EGCG treatment increased phospholipase C (PLC) activity, and the same results were obtained with cGMP inducer treatment. EGCG-induced ASM activation was completely suppressed by pharmacological inhibition of PLC. Collectively, EGCG-induced cGMP activated the cGMP/PLC/PKCO/ASM signaling axis in multiple myeloma cells. (C) 2019 Elsevier Inc. All rights reserved.
引用
收藏
页码:186 / 191
页数:6
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