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Phosphodiesterase 5 inhibitor acts as a potent agent sensitizing acute myeloid leukemia cells to 67‐kDa laminin receptor‐dependent apoptosis
Author(s) -
Kumazoe Motofumi,
Kim Yoonhee,
Bae Jaehoon,
Takai Mika,
Murata Motoki,
Suemasu Yumi,
Sugihara Kaori,
Yamashita Shuya,
Tsukamoto Shuntaro,
Huang Yuhui,
Nakahara Kanami,
Yamada Koji,
Tachibana Hirofumi
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.07.041
Subject(s) - myeloid leukemia , apoptosis , downregulation and upregulation , cancer research , chemistry , phosphodiesterase , protein kinase b , phosphodiesterase inhibitor , leukemia , cyclic guanosine monophosphate , pharmacology , microbiology and biotechnology , biology , immunology , biochemistry , nitric oxide , enzyme , gene , organic chemistry
(−)‐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.