title: Xestospongin C induces monocytic differentiation of HL60 cells through activation of the ERK pathway.
abstract: Xestospongin C (XC), which is a group of macrocyclic bis-1-oxaquinolizidines, is a potent inhibitor of sarcoendoplasmic reticulum calcium transport ATPase and IP3 receptor. Nevertheless, very less information is available regarding whether XC induces AML differentiation. We investigated the potential role of XC in the differentiation of human leukemia HL60 cells and mechanisms underlying XC actin. XC treatment inhibited proliferation by inducing G1-phase cell cycle arrest in the HL60 cells. In addition, XC induced differentiation of HL60 cells into the CD14(+) monocytic lineage, which was indicated by morphological changes, nitroblue tetrazolium reduction assay, and expressions of CD11b and CD14 surface antigens. Our results also showed that XC promotes phagocytic activity and granularity in HL60 cells, suggesting that the cells are functionally activated. Furthermore, XC enhanced tumor necrosis factor (TNF)-α-mediated cytotoxic effect by increasing the numbers of TNF receptors. Moreover, we showed that XC activates extracellular signal-regulated kinase (ERK) pathway in the differentiation stages. Inhibition of ERK activation using PD98059 significantly decreased NBT+HL60 cells induced by XC treatment. Taken together, the results show that XC promotes monocytic differentiation of HL60 cells via ERK pathway activation, suggesting that XC could be a candidate for use as a differentiation-inducing agent for AML treatment.
authors: Department of Biology Education, Daegu University, Jillyang, Gyeongsan, Gyeongbuk 712-714, Republic of Korea.
authors: Dong-Oh
authors: DO
authors: Moon
authors: Yukihiro
authors: Y
authors: Asami
authors: Mun-Ock
authors: MO
authors: Kim
authors: Jae-Hyuk
authors: JH
authors: Jang
authors: Bo Yeon
authors: BY
authors: Kim
authors: Jong Seog
authors: JS
authors: Ahn
authors: Gi-Young
authors: GY
authors: Kim
authors: Sung Gyu
authors: SG
authors: Yun
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D016193:G1 Phase / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D047028:Macrocyclic Compounds / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010080:Oxazoles / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D018950:Lipopolysaccharide Receptors; D047028:Macrocyclic Compounds; D010080:Oxazoles; C511704:xestospongin C; D048049:Extracellular Signal-Regulated MAP Kinases