title: Native musk and synthetic musk ketone strongly induced the growth repression and the apoptosis of cancer cells.
abstract: BACKGROUND
  Musk is widely used in clinical practice for its anti-cancer properties. Here, we treated various types of cancer using musk to determine which cancers are sensitive to musk treatment. We also compared effects of native musk and synthetic musk ketone in cancer cells. Furthermore, we investigated mechanisms underlying effects of musk.
  
  
  METHODS
  Twenty two cancer cell lines were treated with musk. Cell proliferation and apoptosis analyses were carried out. Native musk and synthetic musk ketone were analyzed by gas chromatograph-mass spectrometer (GC-MS) assay. Differentially expressed genes were determined by microarray and quantitative real-time polymerase chain reaction.
  
  
  RESULTS
  Native musk strongly induced the growth repression and the apoptosis in the majority of cancer cell lines in a dose-dependent manner, but distinct types of cancer showed significantly different reactions. Cancer cells which originated from epithelial cells showed higher sensitivity for musk treatment. By contrast, leukaemia and lymphoma cells were not sensitive. GC-MS analysis demonstrated that native musk contains more than 30 contents in which musk ketone is a major component; synthetic musk ketone was consistent with natural musk ketone, and the used sample of synthetic musk ketone contained only sole component. Similar to native musk, synthetic musk ketone induced the growth repression and the apoptosis of cancer cells. Additionally, numerous genes were differentially expressed in lung cancer cells after native musk treatment. These differentially expressed genes were involved in many signalling pathways. Among these pathways, apoptosis-related pathways included interleukin family, tumor necrosis factor family, and MAPK signalling pathway. Native musk and synthetic musk ketone can up-regulate IL-24 (interleukin family) and DDIT3 (MAPK signalling pathway) in lung cancer cells.
  
  
  CONCLUSIONS
  This research provided strong evidence that native musk and synthetic musk ketone can induce the growth repression and the apoptosis of cancer cells. However, the selection of sensitive cancer patient for individualized treatment is a key step in clinical application. Synthetic musk ketone can substitute for native musk to treat cancer patients. Musk might induce the growth repression and the apoptosis of lung cancer cells through up-regulating IL-24 and DDIT3 expressions.
authors.affiliation: Laboratory of Molecular and Experimental Pathology, Kunming Institute of Zoology, Chinese Academy of Sciences, 32 Jiaochang Donglu, Kunming, Yunnan, 650223, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.affiliation: Laboratory of Molecular and Experimental Pathology, Kunming Institute of Zoology, Chinese Academy of Sciences, 32 Jiaochang Donglu, Kunming, Yunnan, 650223, China. caoy@mail.kiz.ac.cn.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology / Q000627:therapeutic use*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D015398:Signal Transduction; D014992:Xylenes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D005229:Fatty Acids, Monounsaturated; D014992:Xylenes; C008563:musk; C031448:musk ketone
keywords: Apoptosis; Cancer; DDIT3; Differentially expressed gene; IL-24; Musk; Musk ketone; Proliferation; Traditional Chinese medicine