Phosphodiesterase 5 inhibitor acts as a potent agent sensitizing acute myeloid leukemia cells to 67-kDa laminin receptor-dependent apoptosis
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- 作者：Motofumi Kumazoe ; Yoonhee Kim ; Jaehoon Bae ; Mika Takai ; Motoki Murata ; Yumi Suemasu ; Kaori Sugihara ; Shuya Yamashita ; Shuntaro Tsukamoto ; Yuhui Huang ; Kanami Nakahara ; Koji Yamada ; Hirofumi Tachibana
- 关键词：67LR ; 67-kDa laminin receptor ; AML ; acute myeloid leukemia ; ASM ; acid sphingomyelinase ; EGCG ; (&minus ; )-epigallocatechin-3-O-gallate ; PDE ; phosphodiesterase
- 刊名：FEBS Letters
- 出版年：2013
- 出版时间：17 September, 2013
- 年：2013
- 卷：587
- 期：18
- 页码：3052-3057
- 全文大小：1054 K
文摘
(?)-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.