title: Induction of apoptosis by obovatol as a novel therapeutic strategy for acute myeloid leukemia.
abstract: Obovatol, a compound isolated from the bark cortex of Magnolia officinalis (cortex Magnoliae officinalis; M. officinalis), has been studied for use in the treatment of solid cancers. However, the mechanisms of action and the effects of obovatol against acute myeloid leukemia (AML) remain unclear and require further investigation. Therefore, this study was conducted using a human AML cell line (MM6). Obovatol increased pro-apoptotic (Bax) and decreased anti-apoptotic (Bcl-2) protein expression, resulting in caspase-3 and caspase-9 activation measured by caspase-Glo 3/7 assay. Furthermore, obovatol activated the mitogen-activated protein kinase (MAPK) signaling pathway [c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38] and inhibited the activation of the nuclear factor-κB (NF-κB) signaling pathway analyzed by western blot analysis. Taken together, these findings provide evidence that obovatol inhibits cell proliferation in AML and induces apoptosis through the activation of the MAPK pathway in addition to the intrinsic apoptotic pathway. In addition, obovatol suppressed the expression of mixed-lineage leukemia (MLL) target genes by inhibiting the activation of the NF-κB pathway. Therefore, these results suggest that obovatol may have potential for use in the treatment of leukemia.
authors.affiliation: School of Life Science, BK21 plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Hyeng-Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: School of Life Science, BK21 plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Ga Young
authors.initials: GY
authors.lastname: Lim
authors.affiliation: School of Life Science, BK21 plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Junmo
authors.initials: J
authors.lastname: Hwang
authors.affiliation: School of Life Science, BK21 plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Zae Young
authors.initials: ZY
authors.lastname: Ryoo
authors.affiliation: School of Life Science, BK21 plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Tae-Lin
authors.initials: TL
authors.lastname: Huh
authors.affiliation: School of Life Science, BK21 plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Sanggyu
authors.initials: S
authors.lastname: Lee
mesh_terms: D000208:Acute Disease; D017209:Apoptosis / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D031566:Magnolia / Q000737:chemistry; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010647:Phenyl Ethers / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D020298:U937 Cells; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D001713:Biphenyl Compounds; D010647:Phenyl Ethers; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C036795:obovatol; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases