title: Apigenin affects leptin/leptin receptor pathway and induces cell apoptosis in lung adenocarcinoma cell line.
abstract: BACKGROUND
  Apigenin, a common edible plant flavonoid, is a well characterised antioxidant. The adipokine leptin exerts proliferative and anti-apoptotic activities in a variety of cell types. In cancer cells, apigenin may induce a pro-apoptotic pathway whereas leptin has an anti-apoptotic role. The purpose of the study is to investigate the role of apigenin and of leptin/leptin receptor pathway on proliferation and on apoptosis in lung adenocarcinoma.
  
  
  METHODS
  Immunocytochemistry, flow cytometry and RT-q-RT PCR, were used to investigate the expression and modulation of leptin receptors on the lung adenocarcinoma cell line A549 in presence or absence of apigenin and of leptin, alone or combined. Clonogenic test to evaluate cell proliferation was assessed. Exogenous leptin binding to its receptors by flow cytometry, reactive oxygen species (ROS) by dichlorofluorescein diacetate analysis, cell death by ethidium bromide and apoptosis by annexin V analysis were assessed. Apoptosis was assessed also in presence of lung adenocarcinoma pleural fluids (PF) (n=6).
  
  
  RESULTS
  A549 express leptin/leptin receptor pathway and its expression is upregulated by apigenin. Apigenin alone or combined with leptin significantly decreases cell proliferation and significantly increases the spontaneous release of ROS, with augmented cell death and apoptosis, this latter also in the presence of lung adenocarcinoma PF. Leptin alone significantly increases cell proliferation and significantly decreases cell death.
  
  
  CONCLUSIONS
  These results strongly suggest the potential utility of the flavonoid apigenin in the complementary therapeutic approach of patients with lung adenocarcinoma.
authors.affiliation: Institute of Biomedicine and Molecular Immunology, National Research Council, Palermo, Italy. andreina@neomedia.it
authors.forename: Andreina
authors.initials: A
authors.lastname: Bruno
authors.forename: Liboria
authors.initials: L
authors.lastname: Siena
authors.forename: Stefania
authors.initials: S
authors.lastname: Gerbino
authors.forename: Maria
authors.initials: M
authors.lastname: Ferraro
authors.forename: Pascal
authors.initials: P
authors.lastname: Chanez
authors.forename: Marco
authors.initials: M
authors.lastname: Giammanco
authors.forename: Mark
authors.initials: M
authors.lastname: Gjomarkaj
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pace
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D047310:Apigenin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D054411:Receptors, Leptin / Q000378:metabolism*
chemical_list: D020738:Leptin; D054411:Receptors, Leptin; D047310:Apigenin