title: Delicaflavone induces autophagic cell death in lung cancer via Akt/mTOR/p70S6K signaling pathway.
abstract: Searching for potential anticancer agents from natural sources is an effective strategy for developing novel chemotherapeutic agents. In this study, data supporting the in vitro and in vivo anticancer effects of delicaflavone, a rarely occurring biflavonoid from Selaginella doederleinii, were reported. Delicaflavone exhibited favorable anticancer properties, as shown by the MTT assay and xenograft model of human non-small cell lung cancer in male BALB/c nude mice without observable adverse effect. By transmission electron microscopy with acridine orange and Cyto-ID®Autophagy detection dyes, Western blot analysis, and RT-PCR assay, we confirmed that delicaflavone induces autophagic cell death by increasing the ratio of LC3-II to LC3-I, which are autophagy-related proteins, and promoting the generation of acidic vesicular organelles and autolysosomes in the cytoplasm of human lung cancer A549 and PC-9 cells in a time- and dose-dependent manner. Delicaflavone downregulated the expression of phospho-Akt, phospho-mTOR, and phospho-p70S6K in a time- and dose-dependent manner, suggesting that it induced autophagy by inhibiting the Akt/mTOR/p70S6K pathway in A549 and PC-9 cells. Delicaflavone is a potential anticancer agent that can induce autophagic cell death in human non-small cell lung cancer via the Akt/mTOR/p70S6K signaling pathway. Delicaflavone showed anti-lung cancer effects in vitro and in vivo. Delicaflavone induced autophagic cell death via Akt/mTOR/p70S6K signaling pathway. Delicaflavone did not show observable side effects in a xenograft mouse model. Delicaflavone may represent a potential therapeutic agent for lung cancer.
  
  
  
  Delicaflavone showed anti-lung cancer effects in vitro and in vivo. Delicaflavone induced autophagic cell death via Akt/mTOR/p70S6K signaling pathway. Delicaflavone did not show observable side effects in a xenograft mouse model. Delicaflavone may represent a potential therapeutic agent for lung cancer.
authors.affiliation: Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, 350108, China.|Department of Pharmacy, Provincial Clinical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, 350001, China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Sui
authors.affiliation: Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, 350108, China. yauhung@126.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Yao
authors.affiliation: Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, 350108, China.
authors.forename: Shaoguang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pathology, Provincial Clinical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, 350001, China.
authors.forename: Long
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of TCM Resource and Apitherapy, Bee Science College, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.
authors.forename: Peiying
authors.initials: P
authors.lastname: Shi
authors.affiliation: Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, 350108, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, 350108, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, 350108, China.
authors.forename: Shilan
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, 350108, China.
authors.forename: Youjia
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, 350108, China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, 350108, China.
authors.forename: Liying
authors.initials: L
authors.lastname: Huang
authors.affiliation: Institute of Nano Medicine Technology, Faculty of Pharmacy, Fujian Medical University, Fuzhou, 350108, China. qicailiu@fjmu.edu.cn.
authors.forename: Qicai
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Analysis, Faculty of Pharmacy, Fujian Medical University, Fuzhou, 350108, China. xhl1963@sina.com.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Lin
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000627:therapeutic use*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D047309:Flavones / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D032503:Selaginellaceae / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D047309:Flavones; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases
keywords: Akt/mTOR/p70S6K signaling pathway; Autophagy; Delicaflavone; Human lung cancer A549 cell; PC-9 cell