title: Capillin, a major constituent of Artemisia capillaris Thunb. flower essential oil, induces apoptosis through the mitochondrial pathway in human leukemia HL-60 cells.
abstract: BACKGROUND
  Natural products are one of the most important sources of drugs used in pharmaceutical therapeutics. Screening of several natural products in the search for novel anticancer agents against human leukemia HL-60 cells led us to identify potent apoptosis-inducing activity in the essential oil fraction from Artemisia capillaris Thunb. flower.
  
  
  METHODS
  The cytotoxic effects of extracts were assessed on human leukemia HL-60 cells by XTT assay. Induction of apoptosis was assessed by analysis of DNA fragmentation and nuclear morphological change. The plant name was checked with the plant list website (http://www.theplantlist.org).
  
  
  RESULTS
  A purified compound from the essential oil fraction from Artemisia capillaris Thunb. flower that potently inhibited cell growth in human leukemia HL-60 cells was identified as capillin. The cytotoxic effect of capillin in cells was associated with apoptosis. When HL-60 cells were treated with 10(-6) M capillin for 6 h, characteristic features of apoptosis such as DNA fragmentation and nuclear fragmentation were observed. Moreover, activation of c-Jun N-terminal kinase (JNK) was detected after treatment with capillin preceding the appearance of characteristic properties of apoptosis. Release of cytochrome c from mitochondria was also observed in HL-60 cells that had been treated with capillin.
  
  
  CONCLUSIONS
  Capillin induces apoptosis in HL-60 cells via the mitochondrial apoptotic pathway, which might be controlled through JNK signaling. Our results indicate that capillin may be a potentially useful anticancer drug that could enhance therapeutic efficacy.
authors.affiliation: Laboratory of Clinical Pharmacy, Showa Pharmaceutical University, Higashi Tamagawa Gakuen, Machida, Tokyo 194-8543, Japan. Electronic address: ymasuda@ac.shoyaku.ac.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Masuda
authors.affiliation: Laboratory of Clinical Pharmacy, Showa Pharmaceutical University, Higashi Tamagawa Gakuen, Machida, Tokyo 194-8543, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Asada
authors.affiliation: Laboratory of Kampo Medicinal Education, Showa Pharmaceutical University, Higashi Tamagawa Gakuen, Machida, Tokyo 194-8543, Japan.
authors.forename: Rei
authors.initials: R
authors.lastname: Satoh
authors.affiliation: Laboratory of Clinical Pharmacy, Showa Pharmaceutical University, Higashi Tamagawa Gakuen, Machida, Tokyo 194-8543, Japan.
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Takada
authors.affiliation: Laboratory of Kampo Medicinal Education, Showa Pharmaceutical University, Higashi Tamagawa Gakuen, Machida, Tokyo 194-8543, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Kitajima
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D019306:Artemisia / Q000737:chemistry; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D053280:Diynes / Q000494:pharmacology*; D035264:Flowers / Q000737:chemistry; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects*; D009822:Oils, Volatile / Q000494:pharmacology*; D010938:Plant Oils / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053280:Diynes; D009822:Oils, Volatile; D010938:Plant Oils; C065814:capillin; D045304:Cytochromes c; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Apoptosis; Artemisia capillaris Thunb.; Capillin (PubChem CID: 10321); Essential oil; HL-60 cells; JNK