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

Jaehoon Bae, Motofumi Kumazoe, Chieri Takeuchi, Shiori Hidaka, Yoshinori Fujimura, Hirofumi Tachibana

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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 (PKCδ) 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/PKCδ/ASM signaling axis in multiple myeloma cells.

Original languageEnglish
Pages (from-to)186-191
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume520
Issue number1
DOIs
Publication statusPublished - Nov 26 2019

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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