Intermedeol isolated from the leaves of Ligularia fischeri var. spiciformis induces the differentiation of human acute promyeocytic leukemia HL-60 Cells.
The present work was performed to investigate the effects of intermedeol on proliferation and differentiation of human leukemia-derived HL-60 cells as well as the underlying mechanisms for these effects. Intermedeol exhibited a potent antiproliferative activity against HL-60 cells. In addition, this compound was found to be a potent inducer for HL-60 cell differentiation as assessed by nitroblue tetrazolium reduction test, esterase activity assay, phagocytic activity assay, morphology change, and expression of CD14 and CD66b surface antigens. These results suggest that intermedeol induces differentiation of human leukemia cells to granulocytes and monocytes/macrophage lineage. Moreover, the expression level of c-myc was down-regulated during intermedeol-dependent HL-60 cell differentiation, whereas p21(CIP1) was up-regulated. Taken together, our results suggest that intermedeol may have potential as a therapeutic agent in human leukemia.
Jeong
Seoung-Hee
SH
Department of Food and Nutrition, Kyung Hee University, Seoul, Korea.
Koo
Seung-Ja
SJ
Choi
Jung-Hye
JH
Park
Jae-Hoon
JH
Ha
Joohun
J
Park
Hee-Juhn
HJ
Lee
Kyung-Tae
KT
D015703:Antigens, CD; D000951:Antigens, Neoplasm / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D015536:Down-Regulation; D005434:Flow Cytometry; D058851:GPI-Linked Proteins; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology* / Q000627:therapeutic use; D010587:Phagocytosis; D008517:Phytotherapy; D018515:Plant Leaves; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012674:Senecio
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; C504120:CEACAM8 protein, human; D015815:Cell Adhesion Molecules; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D058851:GPI-Linked Proteins; C469042:Intermedeol; D018950:Lipopolysaccharide Receptors; D009281:Naphthalenes; D016271:Proto-Oncogene Proteins c-myc