title: 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.
abstract: 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.
authors.affiliation: 1 Department of Pharmacy, College of Pharmacy, Dankook University , Cheonan, Republic of Korea.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Seo
authors.forename: Young-Rak
authors.initials: YR
authors.lastname: Cho
authors.forename: Wooki
authors.initials: W
authors.lastname: Kim
authors.forename: Seok Hyun
authors.initials: SH
authors.lastname: Eom
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D002867:Chromones / Q000494:pharmacology; D031202:Chrysanthemum / Q000737:chemistry*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects*; D035264:Flowers / Q000737:chemistry*; D006027:Glycosides / Q000494:pharmacology*; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D064209:Phytochemicals / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry
chemical_list: D002867:Chromones; D050760:Cyclin-Dependent Kinase Inhibitor p27; D006027:Glycosides; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D064209:Phytochemicals; D051057:Proto-Oncogene Proteins c-akt; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C008282:linarin