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

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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Kumazoe M,Kim Y,Bae J,Takai M,Murata M,Suemasu Y,Sugihara K,Yamashita S,Tsukamoto S,Huang Y,Nakahara K,Yamada K,Tachibana H

doi

10.1016/j.febslet.2013.07.041

subject

Has Abstract

pub_date

2013-09-17 00:00:00

pages

3052-7

issue

18

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(13)00570-X

journal_volume

587

pub_type

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