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|Title:||Synergistic antileukemia effect of genistein and chemotherapy in mouse xenograft model and potential mechanism through MAPK signaling|
Stephen, Wong C.-H.
Fred, Wong W.-S.
|Citation:||Shen, J.,Tai, Y.-C.,Zhou, J.,Stephen, Wong C.-H.,Xie, Z.,Chen, C.-S.,Cheang, P.T.S.,Han, J.-H.,Fred, Wong W.-S.,Khan, M. (2007). Synergistic antileukemia effect of genistein and chemotherapy in mouse xenograft model and potential mechanism through MAPK signaling. Experimental Hematology 35 (1). ScholarBank@NUS Repository. https://doi.org/10.1016/j.exphem.2006.09.007|
|Abstract:||We investigated the antiproliferative effect of genistein, and its antileukemia effect in combination with cytosine arabinoside (ara-C) in acute myeloid leukemia (AML). Optimal dosage of genistein as single agent and in combination with ara-C was first determined in vitro. Genistein demonstrated a dose- and time-dependent inhibition of cell proliferation, induction of apoptosis, and cell-cycle arrest at G2/M phase. Gene-expression profiles revealed mitogen-activated protein kinase (MAPK) signaling as one of the most affected biological pathways. Phosphatidylinositol 3 kinase, protein kinase A, protein kinase C, MAPK kinase 4, KIT, PIM1, and transforming growth factor-β receptor 1, were significantly downregulated by genistein. To test whether genistein could augment the antiproliferation activity of ara-C, two groups of severe combined immunodeficient mice were inoculated with NB4 and HL-60 cells, respectively, followed by treatment with either genistein or combination of genistein and ara-C. The combination treatment significantly inhibited tumor growth, and improved survival of NB4 (p = 0.0031) and HL-60 (p = 0.0007) xenograft mice. Our present study highlighted the schedule-dependent synergistic antileukemia effect of genistein with chemotherapy in both in vitro and in vivo models. This novel combination could potentially be a promising regimen for treatment of AML. © 2007 International Society for Experimental Hematology.|
|Source Title:||Experimental Hematology|
|Appears in Collections:||Staff Publications|
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