RRC ID 44571
著者 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.
タイトル Phosphodiesterase 5 inhibitor acts as a potent agent sensitizing acute myeloid leukemia cells to 67-kDa laminin receptor-dependent apoptosis.
ジャーナル 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.
巻・号 587(18)
ページ 3052-7
公開日 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
引用数 25
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
ヒト・動物細胞 HL60(RCB0041)