Phosphodiesterase 5 inhibitor acts as a potent agent sensitizing acute myeloid leukemia cells to 67-kDa laminin receptor-dependent apoptosis

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)3052-3057
Number of pages6
JournalFEBS Letters
Volume587
Issue number18
DOIs
Publication statusPublished - Sep 17 2013

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Laminin Receptors
Phosphodiesterase 5 Inhibitors
Myeloid Cells
Acute Myeloid Leukemia
Apoptosis
Type 5 Cyclic Nucleotide Phosphodiesterases
Sphingomyelin Phosphodiesterase
Polyphenols
Cell death
Erectile Dysfunction
Tea
Chemical activation
Blood Vessels
Cell Death
Up-Regulation
Acids
epigallocatechin gallate
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Phosphodiesterase 5 inhibitor acts as a potent agent sensitizing acute myeloid leukemia cells to 67-kDa laminin receptor-dependent apoptosis. / Kumazoe, Motofumi; Kim, Yoonhee; Bae, Jaehoon; Takai, Mika; Murata, Motoki; Suemasu, Yumi; Sugihara, Kaori; Yamashita, Shuya; Tsukamoto, Shuntaro; Huang, Yuhui; Nakahara, Kanami; Yamada, Koji; Tachibana, Hirofumi.

In: FEBS Letters, Vol. 587, No. 18, 17.09.2013, p. 3052-3057.

Research output: Contribution to journalArticle

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 2013, 'Phosphodiesterase 5 inhibitor acts as a potent agent sensitizing acute myeloid leukemia cells to 67-kDa laminin receptor-dependent apoptosis', FEBS Letters, vol. 587, no. 18, pp. 3052-3057. https://doi.org/10.1016/j.febslet.2013.07.041
Kumazoe, Motofumi ; Kim, Yoonhee ; Bae, Jaehoon ; Takai, Mika ; Murata, Motoki ; Suemasu, Yumi ; Sugihara, Kaori ; Yamashita, Shuya ; Tsukamoto, Shuntaro ; Huang, Yuhui ; Nakahara, Kanami ; Yamada, Koji ; Tachibana, Hirofumi. / Phosphodiesterase 5 inhibitor acts as a potent agent sensitizing acute myeloid leukemia cells to 67-kDa laminin receptor-dependent apoptosis. In: FEBS Letters. 2013 ; Vol. 587, No. 18. pp. 3052-3057.
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