title: Induction of apoptosis and differentiation by atractylenolide-1 isolated from Atractylodes macrocephala in human leukemia cells.
abstract: Atractylodes macrocephula Koidz (A. macrocephula, also known as Baizhu) is an important ingredient in several traditional Chinese herb complexes for the treatment of abdominal pain and gastroenterology diseases for thousands of years. We previously demonstrated the induction of ROS-mediated apoptosis by methanol extract of A. macrocephula in human leukemia cells. After purification and assessment of those active compounds from A. macrocephula ethanol extracts, in this study, we focused on the major active compound, atractylenolide I (ATL-I). Through MTT assay and morphology observation, we found cytotoxic effect of ATL-I in human K562 chronic myeloblastic leukemia (CML), U937 acute myeloblastic leukemia (AML) and Jurkat T lymphoma cells. In addition, ATL-I-induced apoptosis was demonstrated by sub G1 and fragmented chromosomal DNA detection using flow cytometry, enzyme-linked immunosorbent assay (ELISA) and agarose electrophoresis. Finally, we found ATL-I also induced caspase-3 and caspase-9 activation through the detection of procaspase-3, procaspase-9 and caspase-3 substrate poly(ADP-ribose) polymerase (PARP) by immunoblotting. Interestingly, we found that ATL-I induced not only apoptosis but also differentiation, as upregulation of CD14 and CD68 surface markers and increase of phagocytosis ability were discovered in ATL-I-treated K562 CML and U937 AML cells. Our study thus suggests the potential of developing new leukemia therapies by using ATL-I for leukemia treatment in the future.
authors.affiliation: Department of Bioscience Technology, College of Health Science, Chang Jung Christian University, Tainan 711, Taiwan, ROC.
authors.forename: Huey-Lan
authors.initials: HL
authors.lastname: Huang
authors.affiliation: Department of Biological Science and Technology, Meiho University, 23 Ping Kuang Road, Neipu Hsiang, Pingtung 912, Taiwan, ROC.
authors.forename: Tzu-Wen
authors.initials: TW
authors.lastname: Lin
authors.affiliation: National Research Institute of Chinese Medicine, Taipei 112, Taiwan, ROC.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Huang
authors.affiliation: Department of Biological Science and Technology, Meiho University, 23 Ping Kuang Road, Neipu Hsiang, Pingtung 912, Taiwan, ROC. Electronic address: x00002093@meiho.edu.tw.
authors.forename: Ray-Ling
authors.initials: RL
authors.lastname: Huang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D031174:Atractylodes / Q000737:chemistry*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007938:Leukemia / Q000473:pathology*; D015394:Molecular Structure; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007783:Lactones; D012717:Sesquiterpenes; C424804:atractylenolide I
keywords: Apoptosis; Atractylenolide I; Atractylodes macrocephula; Baizhu; Differentiation