RRC ID |
44571
|
Author |
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.
|
Title |
Phosphodiesterase 5 inhibitor acts as a potent agent sensitizing acute myeloid leukemia cells to 67-kDa laminin receptor-dependent apoptosis.
|
Journal |
FEBS Lett
|
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.
|
Volume |
587(18)
|
Pages |
3052-7
|
Published |
2013-9-17
|
DOI |
10.1016/j.febslet.2013.07.041
|
PII |
S0014-5793(13)00570-X
|
PMID |
23916810
|
MeSH |
Apoptosis / drug effects*
Catechin / analogs & derivatives*
Catechin / pharmacology
Cyclic GMP / metabolism
Cyclic Nucleotide Phosphodiesterases, Type 5 / genetics
Cyclic Nucleotide Phosphodiesterases, Type 5 / metabolism
Drug Synergism
Enzyme Activation / drug effects
Gene Expression Regulation, Leukemic / drug effects*
HL-60 Cells
Humans
Leukemia, Myeloid, Acute / drug therapy
Leukemia, Myeloid, Acute / genetics
Leukemia, Myeloid, Acute / metabolism
Leukemia, Myeloid, Acute / pathology
Nitric Oxide Synthase Type III / genetics
Nitric Oxide Synthase Type III / metabolism
Oncogene Protein v-akt / genetics
Oncogene Protein v-akt / metabolism
Phosphodiesterase 5 Inhibitors / pharmacology*
Primary Cell Culture
Receptors, Laminin / agonists
Receptors, Laminin / genetics*
Receptors, Laminin / metabolism
Signal Transduction
Sphingomyelin Phosphodiesterase / genetics
Sphingomyelin Phosphodiesterase / metabolism
|
IF |
3.057
|
Times Cited |
25
|
WOS Category
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
Resource |
Human and Animal Cells |
HL60(RCB0041) |