title: Hesperetin impairs glucose uptake and inhibits proliferation of breast cancer cells.
abstract: The flavanone hesperetin is known to decrease basal glucose uptake, although the inhibitory mechanism is largely unknown. Here, we used MDA-MB-231 breast cancer cells to investigate the molecular pathways affected by hesperetin. The results indicate that the suppression of glucose uptake is caused by the down-regulation of glucose transporter 1 (GLUT1). Hesperetin was also found to inhibit insulin-induced glucose uptake through impaired cell membrane translocation of glucose transporter 4 (GLUT4). In addition, the phosphorylation of the insulin receptor-beta subunit (IR-beta) and Akt was suppressed. Hesperetin also decreased cellular proliferation, which is likely due to the inhibition of glucose uptake. Cancer cells are highly dependent on glucose and hesperetin may, therefore, have potential application as an anticancer agent.
authors.affiliation: Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, TX, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.forename: Joy
authors.initials: J
authors.lastname: Wolfram
authors.forename: Kathryn
authors.initials: K
authors.lastname: Boom
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Fang
authors.forename: Haifa
authors.initials: H
authors.lastname: Shen
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D047309:Flavones / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006569:Hesperidin / Q000494:pharmacology*; D006801:Humans; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D015703:Antigens, CD; D000972:Antineoplastic Agents, Phytogenic; D047309:Flavones; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; C495677:SLC2A1 protein, human; C495692:SLC2A4 protein, human; D006569:Hesperidin; C435941:INSR protein, human; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; C013015:hesperetin