title: Acanthoic acid induces cell apoptosis through activation of the p38 MAPK pathway in HL-60 human promyelocytic leukaemia.
abstract: The present study was designed to evaluate the molecular mechanisms of the action of acanthoic acid (ACAN) from Acanthopanax koreanum (Araliaceae) against HL-60 human promyelocytic leukaemia cells. ACAN reduced the proliferation of HL-60 cells in a dose- and time-dependent manner accompanied by the induction of apoptosis. Possible mechanisms of ACAN-induced apoptosis were also examined. The results showed that ACAN-induced the phosphorylation of members of the mitogen-activated protein kinase (MAPK) family, c-Jun N-terminal kinase (JNK), p38 MAPK (p38), and extracellular signal-regulated kinase (ERK). A specific p38 MAPK inhibitor (SB203580) significantly blocked ACAN-induced apoptosis and cell viability, whereas an ERK inhibitor (PD98059) and JNK inhibitor (SP600125) had no effect. Moreover, ACAN induced the cleavage of caspase-3 and poly-ADP-ribose polymerase (PARP), and decreased the level of Bcl-xL, but these effects were inhibited by SB203580 pre-treatment. These results strongly suggest that ACAN may have cancer chemopreventive and therapeutic potential, due to its ability to activate the p38 MAPK-mediated signalling pathways.
authors.affiliation: Jeju center, Korea Basic Science Institute (KBSI), Jeju 690-140, Republic of Korea.
authors.forename: Kil-Nam
authors.initials: KN
authors.lastname: Kim
authors.forename: Young Min
authors.initials: YM
authors.lastname: Ham
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Moon
authors.forename: Min-Jin
authors.initials: MJ
authors.lastname: Kim
authors.forename: Yong-Hwan
authors.initials: YH
authors.lastname: Jung
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Nam Ho
authors.initials: NH
authors.lastname: Lee
authors.forename: Nalae
authors.initials: N
authors.lastname: Kang
authors.forename: Hye-Mi
authors.initials: HM
authors.lastname: Yang
authors.forename: Daekyung
authors.initials: D
authors.lastname: Kim
authors.forename: Chang-Gu
authors.initials: CG
authors.lastname: Hyun
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D028001:Eleutherococcus / Q000737:chemistry*; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D004224:Diterpenes; D010936:Plant Extracts; C099958:acanthoic acid; D048051:p38 Mitogen-Activated Protein Kinases