title: The inhibitory effects of 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone on human colon cancer cells.
abstract: METHODS
  Previously, we reported that 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone (5HHMF), a polymethoxyflavone found in citrus peels, potently inhibited the growth of multiple human colon cancer cells. Herein, we further investigated the anti-cancer mechanisms of 5HHMF in human colon cancer cells.
  
  
  RESULTS
  Colony formation assay revealed that 5HHMF dose dependently inhibited colony formation of multiple colon cancer cells. Western blot analysis demonstrated 5HHMF decreased nuclear β-catenin levels and increased the E-cadherin level in a dose-dependent manner. 5HHMF also modified plasma membrane-associated proteins, such as K-Ras, EGFR, and their downstream effectors, such as Akt. Moreover, treatments with 5HHMF inhibited nuclear translocation of NF-κB, which may contribute to its anti-cancer effects. Add-back study showed that the inhibitory effect of 5HHMF was not associated with the production of reactive oxygen species (ROS). In addition, 5HHMF treatment inhibited the capillary tube formation of human umbilical vein endothelial cells (HUVECs) on matrigel, suggesting a potential anti-tumor angiogenesis effect.
  
  
  CONCLUSIONS
  Our results demonstrated that 5HHMF suppressed multiple oncogenic molecular events in colon cancer cells.
authors.affiliation: Department of Food Science, University of Massachusetts, Amherst, MA, USA.
authors.forename: Peiju
authors.initials: P
authors.lastname: Qiu
authors.forename: Huashi
authors.initials: H
authors.lastname: Guan
authors.forename: Ping
authors.initials: P
authors.lastname: Dong
authors.forename: Shanshan
authors.initials: S
authors.lastname: Guo
authors.forename: Jinkai
authors.initials: J
authors.lastname: Zheng
authors.forename: Shiming
authors.initials: S
authors.lastname: Li
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.forename: Chi-Tang
authors.initials: CT
authors.lastname: Ho
authors.forename: Min-Hsiung
authors.initials: MH
authors.lastname: Pan
authors.forename: David Julian
authors.initials: DJ
authors.lastname: McClements
authors.forename: Hang
authors.initials: H
authors.lastname: Xiao
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000378:metabolism; D047309:Flavones / Q000494:pharmacology*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D051058:Oncogene Protein v-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D015820:Cadherins; D047309:Flavones; D008565:Membrane Proteins; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D051176:beta Catenin; C521815:5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone; C512478:EGFR protein, human; D066246:ErbB Receptors; D051058:Oncogene Protein v-akt