title: Oroxylin A sensitizes non-small cell lung cancer cells to anoikis via glucose-deprivation-like mechanisms: c-Src and hexokinase II.
abstract: BACKGROUND
  Cellular metabolism, particularly glycolysis, is altered during the metastatic process and is highly associated with tumor progression and apoptosis resistance. Oroxylin A, a natural plant flavonoid, exhibits chemopreventive and therapeutic anti-inflammatory and anticancer potential. However, the anticancer effects of oroxylin A on non-small cell lung carcinoma (NSCLC) remain poorly understood.
  
  
  METHODS
  In vitro studies were performed using 2D and 3D conditions. The effects on anoikis-sensitization and glycolysis-inhibition of oroxylin A in human non-small cell lung cancer A549 cells were examined. In vivo murine lung metastasis experiments were utilized to assess the anti-metastatic capacity of oroxylin A.
  
  
  RESULTS
  ROS-mediated activation of c-Src following detachment caused anoikis resistance in A549 cells. Oroxylin A sensitized A549 cells to anoikis by inactivating the c-Src/AKT/HK II pathway in addition to inducing the dissociation of HK II from mitochondria. Prior to sensitizing A549 cells to anoikis, oroxylin A decreased the ATP level and inhibited glycolysis. Furthermore, oroxylin A inhibited lung metastasis of A549 cells in vivo in nude mice.
  
  
  CONCLUSIONS
  Oroxylin A sensitized anoikis, which underlies distinct glucose-deprivation-like mechanisms that involved c-Src and HK II.
  
  
  CONCLUSIONS
  The findings in this study indicated that oroxylin A could potentially be utilized in the development of improved metastatic cancer treatments.
authors.affiliation: China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Libin
authors.initials: L
authors.lastname: Wei
authors.forename: Qinsheng
authors.initials: Q
authors.lastname: Dai
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Zhou
authors.forename: Meijuan
authors.initials: M
authors.lastname: Zou
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Li
authors.forename: Na
authors.initials: N
authors.lastname: Lu
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Guo
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D023102:Anoikis / Q000187:drug effects*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000081247:CSK Tyrosine-Protein Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005419:Flavonoids / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D006593:Hexokinase / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; C080669:5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one; D000255:Adenosine Triphosphate; D006593:Hexokinase; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D005947:Glucose