title: Evaluation of nitric oxide donors impact on cisplatin resistance in various ovarian cancer cell lines.
abstract: Ovarian cancer chemoresistance, both intrinsic and acquired, is the main obstacle in improving the outcome of anticancer therapies. Therefore the development of new treatment strategies, including the use of new compounds that can support the standard therapeutics is required. Among many candidates, nitric oxide (NO) donors, agents with multivalent targeted activities in cancer cells, are worth considering. The aim of this study was evaluation of SPER/NO and DETA/NO ability to enhance cisplatin cytotoxicity against different ovarian cancer cell lines. Obtained data indicate that NO donors action varies between different cancer cell lines and is strongest in low aggressive and cisplatin sensitive cells. While statistically significant, the enhancement of cisplatin cytotoxicity by NO donors is of low magnitude. The rise in the percentage of late apoptotic/necrotic ovarian cancer cells may suggest that NO donors enhancement action might be based on the cellular ATP depletion. Nevertheless, no significant impact of the NO donors, cisplatin or their combination on the expressions of ABCB1, BIRC5 and PTEN genes has been found. Although our data puts the therapeutical potential of NO donors to aid cisplatin action in question it may also point out at the further approach to utilize these compounds in therapies.
authors.affiliation: Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Kielbik
authors.affiliation: Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Szulc-Kielbik
authors.affiliation: Department of Gynecology and Gynecologic Oncology, Polish Mother's Memorial Hospital-Research Institute, Lodz, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Nowak
authors.affiliation: Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Sulowska
authors.affiliation: Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland. Electronic address: mklink@cbm.pan.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Klink
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010051:Ovarian Neoplasms; D051059:PTEN Phosphohydrolase / Q000235:genetics; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077022:Survivin; D014226:Triazenes / Q000494:pharmacology*
chemical_list: C105351:1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene; C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D020030:Nitric Oxide Donors; D000077022:Survivin; D014226:Triazenes; C091861:spermine nitric oxide complex; D013096:Spermine; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D002945:Cisplatin
keywords: Chemoresistance; Cisplatin; Nitric oxide donors; Ovarian cancer cells