title: Hinesol, a compound isolated from the essential oils of Atractylodes lancea rhizome, inhibits cell growth and induces apoptosis in human leukemia HL-60 cells.
abstract: Hinesol is a unique sesquiterpenoid isolated from the Chinese traditional medicine, Atractylodes lancea rhizome. In a previous study, we screened various natural products in human leukemia HL-60 cells and identified an essential oil fraction from A. lancea rhizome that exhibited apoptosis-inducing activity in these cells; hinesol was subsequently shown to be the compound responsible for this apoptosis-inducing activity. In this study, we describe the cytotoxic effects and molecular mechanisms of hinesol in HL-60 cells. The antitumor effect of hinesol was associated with apoptosis. When HL-60 cells were treated with hinesol, characteristic features of apoptosis, such as nuclear fragmentation and DNA fragmentation, were observed. These growth-inhibitory and apoptosis-inducing activities of hinesol in leukemia cells were much stronger than those of β-eudesmol, another compound isolated from the essential oil fraction. Furthermore, hinesol induced activation of c-Jun N-terminal kinase (JNK), but not p38, prior to the onset of apoptosis. These results suggested that hinesol induced apoptosis through the JNK signaling pathway in HL-60 cells. Therefore, hinesol may represent a novel medicinal drug having indications in the treatment of various cancers, including leukemia.
authors.affiliation: Laboratory of Clinical Pharmacy, Showa Pharmaceutical University, Higashi Tamagawa Gakuen, Machida, Tokyo, 194-8543, Japan, ymasuda@ac.shoyaku.ac.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Masuda
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kadokura
authors.forename: Maki
authors.initials: M
authors.lastname: Ishii
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Takada
authors.forename: Junichi
authors.initials: J
authors.lastname: Kitajima
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D031174:Atractylodes / Q000737:chemistry*; D002453:Cell Cycle; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007938:Leukemia; D020935:MAP Kinase Signaling System; D009822:Oils, Volatile / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D027343:Rhizome / Q000737:chemistry*; D012717:Sesquiterpenes / Q000494:pharmacology*; D013141:Spiro Compounds / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D009822:Oils, Volatile; D010936:Plant Extracts; D012717:Sesquiterpenes; D013141:Spiro Compounds; C065858:hinesol; D048031:JNK Mitogen-Activated Protein Kinases
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