title: Blockade of the Ras/Raf/ERK and Ras/PI3K/Akt Pathways by Monacolin K Reduces the Expression of GLO1 and Induces Apoptosis in U937 Cells.
abstract: Monacolin K, a hydrolytic product of icaritin, is the major active component in the traditional fermented Monascus purpureus. Monacolin K inhibits the proliferation of acute myeloid leukemia (AML), but underlying mechanisms remain to be identified. The present study demonstrates that monacolin K inhibits the proliferation of human AML cell line U937 in a dose-dependent manner. Importantly, morphological, DNA fragmentation, and image cytometry analyses indicated that monacolin K induced U937 cell apoptosis. Monacolin K could inactivate Ras translocation from cytosol to cell membrane. Monacolin K could also reduce the Ras-dependent phosphorylation of ERK and Akt, and the subsequent translocation of nuclear factor kappa B (NF-κB) from cytosol to nucleus in U937 cells. The underlying mechanisms of apoptotic activity of monacolin K were associated with inhibition of the Ras/Raf/ERK and Ras/PI3K/Akt signals and down-regulation of HMG-CoA reductase and glyoxalase 1. On the basis of results obtained using specific inhibitors U0126, LY294002, and JSH-23, the Ras/Raf/ERK/NF-κB/GLO1 and Ras/Akt/NF-κB/GLO1 pathways were proposed for the apoptotic effect of monacolin K in U937 cells.
authors.affiliation: Department of Food Science, National Pingtung University of Science and Technology , Pingtung 91201, Taiwan.
authors.forename: Chun-Chia
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Food Science, National Pingtung University of Science and Technology , Pingtung 91201, Taiwan.
authors.forename: Mei-Li
authors.initials: ML
authors.lastname: Wu
authors.affiliation: Department of Food Science, Rutgers University , New Brunswick, New Jersey 08901, United States.
authors.forename: Chi-Tang
authors.initials: CT
authors.lastname: Ho
authors.affiliation: Department of Food Science, National Pingtung University of Science and Technology , Pingtung 91201, Taiwan.
authors.forename: Tzou-Chi
authors.initials: TC
authors.lastname: Huang
keywords: HMG-CoA reductase; acute myeloid leukemia; apoptosis; glyoxalase 1; inactivate Ras translocation; monacolin K