論文 - 詳細
RRC ID | 44571 |
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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) |