title: Induction of human leukemia cell differentiation via PKC/MAPK pathways by arsantin, a sesquiterpene lactone from Artemisia santolina.
abstract: Sesquiterpene lactone compounds have received considerable attention in pharmacological research due to their therapeutic effects including anti-cancer and anti-inflammatory activities. In this report, we investigated the effect of arsantin, a sesquiterpene lactone compound present in Artemisia santolina, on cellular differentiation in the human promyelocytic leukemia HL-60 cell culture system. Arsantin significantly induced HL-60 cell differentiation in a concentration-dependent manner. Cytofluorometric analysis indicated that arsantin induced HL-60 cell differentiation predominantly into granulocytes. Both PKC and MAPK inhibitors suppressed the HL-60 cell differentiation induced by arsantin. Moreover, treatment with arsantin increased protein levels of PKCα and PKCβII isoforms, and also induced increased protein levels and phosphorylation form of MAPKs in HL-60 cells. Importantly, arsantin synergistically enhanced differentiation of HL-60 cells in a dose-dependent manner when combined with either low doses of 1,25-(OH)2D3 or ATRA. The ability to enhance the differentiation potential of 1,25-(OH)2D3 or ATRA by arsantin may improve outcomes in the therapy of acute promyelocytic leukemia.
authors.affiliation: Division of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, 136-701, Republic of Korea.
authors.forename: Sin Ho
authors.initials: SH
authors.lastname: Kweon
authors.affiliation: Division of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, 136-701, Republic of Korea.
authors.forename: Ju Han
authors.initials: JH
authors.lastname: Song
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Kwangju, 500-757, Republic of Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Division of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, 136-701, Republic of Korea. tskim@korea.ac.kr.
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Kwangju, 500-757, Republic of Korea. bgchoi@jnu.ac.kr.
authors.forename: Bo Gil
authors.initials: BG
authors.lastname: Choi
mesh_terms: D019306:Artemisia / Q000737:chemistry*; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D018922:HL-60 Cells; D006801:Humans; D007783:Lactones / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D007783:Lactones; D012717:Sesquiterpenes; C000610364:arsantin; D014212:Tretinoin; D011493:Protein Kinase C; D002117:Calcitriol
keywords: Arsantin; HL60 differentiation; MAPK; Protein kinase C; Sesquiterpene lactone