title: Nitric oxide donors reduce the invasion ability of ovarian cancer cells in vitro.
abstract: The most important factors involved in tumor metastasis and angiogenesis are metalloproteinases (MMPs), vascular endothelial growth factor, and multifunctional transforming growth factor β1. These factors are responsible for extracellular matrix degradation, induction of vascular permeability, and enhancement of tumor cells' invasion and metastasis. Elevated expression and secretion of the above-mentioned factors are correlated with the higher aggressiveness of tumors and low patient survival for example, patients with ovarian cancer. Therefore, regulation of the expression, secretion, and activity of these factors is still considered a potent target for therapeutic intervention in cancer patients. Nitric oxide (NO) donors belong to the class of agents with multivalent targeted activities in cancer cells and are considered potential anticancer therapeutics. Our studies have shown that NO donors such as spermine/NO and diethylenetriamine/NO decrease the secretion of vascular endothelial growth factor-A from the OVCAR-3 ovarian cancer cell line, but not from the SK-OV-3 ovarian cancer cell line. The release of MMP-2 from both cell lines was reduced in a soluble guanylate cyclase-dependent manner by spermine/NO and diethylenetriamine/NO. Nevertheless, MMP-2 activity was only affected in SK-OV-3 cells. Both NO donors reduced the transmigration of the ovarian cancer cell lines. We did not observe any significant effect of spermine/NO and diethylenetriamine/NO on mRNA expression of the tested aggressiveness factors. In conclusion, our data indicated that NO donors reduced the metastatic potential of ovarian cancer cells, but its impact is rather low and requires high concentrations of donors. Moreover, both the tested cell lines differed in the susceptibility to NO donors.
authors.affiliation: aInstitute of Medical Biology, Polish Academy of Sciences bDepartment of Gynecology and Gynecologic Oncology, Polish Mother's Memorial Hospital-Research Institute, Lodz, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Kielbik
authors.forename: Izabela
authors.initials: I
authors.lastname: Szulc
authors.forename: Marta
authors.initials: M
authors.lastname: Brzezinska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bednarska
authors.forename: Patrycja
authors.initials: P
authors.lastname: Przygodzka
authors.forename: Zofia
authors.initials: Z
authors.lastname: Sulowska
authors.forename: Marek
authors.initials: M
authors.lastname: Nowak
authors.forename: Magdalena
authors.initials: M
authors.lastname: Klink
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000473:pathology*; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D053773:Transforming Growth Factor beta1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C091861:spermine nitric oxide complex; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; D013096:Spermine; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9