Phytochemical linarin enriched in the flower of Chrysanthemum indicum inhibits proliferation of A549 human alveolar basal epithelial cells through suppression of the Akt-dependent signaling pathway

J Med Food. 2013 Dec;16(12):1086-94. doi: 10.1089/jmf.2012.2674. Epub 2013 Oct 11.


In this study, we report the anti-proliferative effect and molecular mechanism of Chrysanthemum indicum (C. indicum) on A549 human alveolar basal epithelial cells. We also analyzed the changes in C. indicum component profiles due to modifications of predrying process, flower size, and extraction method. Among the varieties of modifications tested, high-temperature heat dry (HTD) of small flower biotype followed by the methanolic extraction resulted in the strongest anti-proliferative activity of C. indicum extract in A549 cells. High-performance liquid chromatography of C. indicum revealed that the levels of acacetin 7-O-rutinoside (linarin) are markedly increased by heat treatment, especially HTD. Finally, we showed that linarin-mediated inhibition of cell proliferation is associated with suppression of Akt activation and induction of cyclin-dependent kinase inhibitor p27(Kip1) as evidenced by cell cycle analysis and treatment with LY294002, an inhibitor of phosphatidylinositol 3-kinase/Akt pathway. Taken together, these findings suggest the need for further development and evaluation of linarin from C. indicum for the treatment and prevention of lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Chromatography, High Pressure Liquid
  • Chromones / pharmacology
  • Chrysanthemum / chemistry*
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Epithelial Cells / drug effects*
  • Flowers / chemistry*
  • Glycosides / pharmacology*
  • Humans
  • Morpholines / pharmacology
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Phytochemicals / pharmacology*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Tandem Mass Spectrometry


  • Chromones
  • Glycosides
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Phytochemicals
  • Cyclin-Dependent Kinase Inhibitor p27
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Proto-Oncogene Proteins c-akt
  • linarin