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

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.

Keywords: (−)-epigallocatechin-3-O-gallate; 67-kDa laminin receptor; 67LR; AML; ASM; Acid sphingomyelinase; Acute myeloid leukemia; Apoptosis; EGCG; Epigallocatechin-3-O-gallate; Laminin receptor; PDE; acid sphingomyelinase; acute myeloid leukemia; cGMP; phosphodiesterase.