title: Modulation of cisplatin sensitivity in human ovarian carcinoma A2780 and SKOV3 cell lines by sulforaphane.
abstract: Cisplatin resistance is one of the major obstacles in the treatment of ovarian cancer. In an effort to look for new possibilities of how to overcome this difficulty, we studied the mechanisms of the interactions between sulforaphane (SFN) and cisplatin (cisPt) in combined treatment of human ovarian carcinoma A2780 and SKOV3 cell lines. Synergy (A2780) and antagonism (SKOV3) found in MTT assay was confirmed by apoptosis. While SFN significantly potentiated cisPt-induced DNA damage in A2780 cells, it protected SKOV3 cells against cisPt-crosslinking. We revealed a less efficient Nrf-2 pathway inducibility by SFN in A2780 compared to SKOV3 cells, when activation of the Nrf-2 pathway incites its protectivity against cisPt. Thus, different activation of the Nrf-2 pathway may explain the dual effects of SFN.
authors.affiliation: Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833 91 Bratislava, Slovak Republic. Electronic address: exonhun@savba.sk.
authors.forename: Luba
authors.initials: L
authors.lastname: Hunakova
authors.affiliation: Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833 91 Bratislava, Slovak Republic.
authors.forename: Paulina
authors.initials: P
authors.lastname: Gronesova
authors.affiliation: Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833 91 Bratislava, Slovak Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Horvathova
authors.affiliation: Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833 91 Bratislava, Slovak Republic.
authors.forename: Ivan
authors.initials: I
authors.lastname: Chalupa
authors.affiliation: Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833 91 Bratislava, Slovak Republic.
authors.forename: Dana
authors.initials: D
authors.lastname: Cholujova
authors.affiliation: Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833 91 Bratislava, Slovak Republic.
authors.forename: Jozef
authors.initials: J
authors.lastname: Duraj
authors.affiliation: Cancer Research Institute, Slovak Academy of Sciences, Vlarska 7, 833 91 Bratislava, Slovak Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Sedlak
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D015398:Signal Transduction; D013454:Sulfoxides
chemical_list: D000970:Antineoplastic Agents; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D013454:Sulfoxides; C016766:sulforaphane; D002945:Cisplatin
keywords: Chromosomal aberrations; Cisplatin; Cytotoxicity, human ovarian carcinoma cells; Nrf-2 pathway; Sulforaphane