Phosphodiesterase 5 inhibitor acts as a potent agent sensitizing acute myeloid leukemia cells to 67-kDa laminin receptor-dependent apoptosis

Motofumi Kumazoe, Yoonhee Kim, Jaehoon Bae, Mika Takai, Motoki Murata, Yumi Suemasu, Kaori Sugihara, Shuya Yamashita, Shuntaro Tsukamoto, Yuhui Huang, Kanami Nakahara, Koji Yamada, Hirofumi Tachibana

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

(-)-Epigallocatechin-3-O-gallate (EGCG), a polyphenol in green tea, induces apoptosis in acute myeloid leukemia (AML) cells without affecting normal cells. In this study, we observed that cGMP acts as a cell death mediator of the EGCG-induced anti-AML effect through acid sphingomyelinase activation. EGCG activated the Akt/eNOS axis, a well-known mechanism in vascular cGMP upregulation. We also observed that a major cGMP negative regulator, phosphodiesterase 5, was overexpressed in AML cells, and PDE5 inhibitor, an anti-erectile dysfunction drug, synergistically enhanced the anti-AML effect of EGCG. This combination regimen killed AML cells via overexpressed 67-kDa laminin receptors.

Original languageEnglish
Pages (from-to)3052-3057
Number of pages6
JournalFEBS Letters
Volume587
Issue number18
DOIs
Publication statusPublished - Sep 17 2013

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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