Phosphodiesterase 5 inhibitor acts as a potent agent sensitizing acute myeloid leukemia cells to 67-kDa laminin receptor-dependent apoptosis |
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| Authors: | 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 |
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| Institution: | 1. Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan;2. Food Functional Design Research Center, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan |
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| 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. |
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| Keywords: | 67LR 67-kDa laminin receptor AML acute myeloid leukemia ASM acid sphingomyelinase EGCG (&minus )-epigallocatechin-3-O-gallate PDE phosphodiesterase |
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