title: Progesterone and estrogen prevent cisplatin-induced apoptosis of lung cancer cells.
abstract: Metastatic non-small cell lung cancer (NSCLC) remains the most common cause of tumor mortality despite the introduction of novel agents. Female sex hormones play a role in NSCLC pathogenesis and negatively influence the course of this disease. Herein, we present data on possible underlying mechanisms. Both estrogen and progesterone pre-treatment led to chemoresistance of A549 NSCLC cells in vitro by attenuating cisplatin-induced apoptosis. These effects were not antagonized by the estrogen or progesterone receptor antagonists ICI 182,780 and RU486 (mifepristone). Cisplatin induced apoptosis via activation of caspases -3/7, -8 and -9. Estrogen and progesterone attenuated levels of caspase activation. Interestingly, copper-transporter-1, which is responsible for the intracellular accumulation of cisplatin, was not modulated by sex hormones and the effects of estrogen and progesterone were neither additive nor synergistic. Our results suggest that estrogen and progesterone contribute to the development of chemotherapy resistance in NSCLC via non-classical sex hormone signaling pathways.
authors.affiliation: Otfried-Mueller Str. 10, D-72076 Tuebingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Grott
authors.forename: Serkan
authors.initials: S
authors.lastname: Karakaya
authors.forename: Frank
authors.initials: F
authors.lastname: Mayer
authors.forename: Fabian
authors.initials: F
authors.lastname: Baertling
authors.forename: Cordian
authors.initials: C
authors.lastname: Beyer
authors.forename: Markus
authors.initials: M
authors.lastname: Kipp
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Kopp
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D027682:Cation Transport Proteins / Q000502:physiology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D000079923:Copper Transporter 1; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004967:Estrogens / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011374:Progesterone / Q000494:pharmacology*
chemical_list: D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; D004967:Estrogens; C490079:SLC31A1 protein, human; D011374:Progesterone; D020169:Caspases; D002945:Cisplatin