title: Chronic-leptin attenuates Cisplatin cytotoxicity in MCF-7 breast cancer cell line.
abstract: OBJECTIVE
  Large-scale epidemiological studies support a correlation between obesity and breast cancer in postmenopausal women. Circulating leptin levels are increased in obese and it has been suggested to play a significant role in mammary tumor formation and progression. Moreover, regulation of oxidative stress is another important factor in both tumor development and responses to anticancer therapies. The aim of this study was to examine the relationship between oxidative stress and chronic leptin exposure.
  
  
  METHODS
  We treated MCF-7 breast cancer cells with 100 ng/mL leptin for 10 days and analyzed cell growth, ROS production and oxidative damage, as well as, some of the main antioxidant systems. Furthermore, since the hyperleptinemia has been associated with a worse pathology prognosis, we decided to test the influence of leptin in response to cisplatin anticancer treatment.
  
  
  RESULTS
  Leptin signalling increased cell proliferation but reduced ROS production, as well as, oxidative damage. We observed an upregulation of SIRT1 after leptin exposure, a key regulator of stress response and metabolism. Additionally, leptin counteracted cisplatin-induced cytotoxicity in tumor cells, showing a decrease in cell death.
  
  
  CONCLUSIONS
  Chronic leptin could contribute to the effective regulation of endogenous and treatment-induced oxidative stress, and it contributes to explain in part its proliferative effects.
authors.affiliation: Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS-IdISPa), Universitat de les IllesBalears, E07122 Palma de Mallorca, Illes Balears, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Nadal-Serrano
authors.forename: Jorge
authors.initials: J
authors.lastname: Sastre-Serra
authors.forename: Adamo
authors.initials: A
authors.lastname: Valle
authors.forename: Pilar
authors.initials: P
authors.lastname: Roca
authors.forename: Jordi
authors.initials: J
authors.lastname: Oliver
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology*; D061986:MCF-7 Cells / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D020738:Leptin; D017382:Reactive Oxygen Species; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D002945:Cisplatin