title: Nobiletin suppresses the proliferation and induces apoptosis involving MAPKs and caspase-8/-9/-3 signals in human acute myeloid leukemia cells.
abstract: Nobiletin, a compound isolated from citrus fruits, is a polymethoxylated flavone derivative that was shown to have anti-inflammatory and anticancer activities in various solid tumors. The anticancer effect of nobiletin on nonsolid tumor remains unclear. Herein, the molecular mechanisms by which nobiletin exerts its anticancer effects on acute myeloid leukemia (AML) cells were investigated. The results showed that nobiletin suppressed cell proliferation in various types of AML cell lines. Moreover, nobiletin induced cell-cycle arrest of HL-60 AML cells at the G0/G1 phase by suppressing extracellular signal-regulated kinase (ERK) activity. Furthermore, nobiletin effectively induced apoptosis of HL-60 cells through caspase-8, caspase-9, and caspases-3 activation concomitantly with a marked induction of p38 mitogen-activated protein kinase (MAPK) activation, but without affecting expression levels of Bcl-2, Bax, or Bid. Taken together, our results suggest that nobiletin inhibited HL-60 cell proliferation through inducing cell-cycle arrest and apoptosis and could serve as a potential additional chemotherapeutic agent for treating AML.
authors.affiliation: School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Pei-Ching
authors.initials: PC
authors.lastname: Hsiao
authors.forename: Wei-Jiunn
authors.initials: WJ
authors.lastname: Lee
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.forename: Peng
authors.initials: P
authors.lastname: Tan
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Chen
authors.forename: Liang-Ming
authors.initials: LM
authors.lastname: Lee
authors.forename: Junn-Liang
authors.initials: JL
authors.lastname: Chang
authors.forename: Gi-Ming
authors.initials: GM
authors.lastname: Lai
authors.forename: Jyh-Ming
authors.initials: JM
authors.lastname: Chow
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Chien
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047309:Flavones / Q000494:pharmacology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D047309:Flavones; C008661:nobiletin; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9