title: Nitric oxide donor augments antineoplastic effects of arginine deprivation in human melanoma cells.
abstract: Anticancer therapy based on recombinant arginine-degrading enzymes has been proposed for the treatment of several types of malignant cells deficient in arginine biosynthesis. One of the predicted side effects of such therapy is restricted bioavailability of nitric oxide as arginine catabolic product. Prolonged NO limitation may lead to unwanted disturbances in NO-dependent vasodilation, cardiovascular and immune systems. This problem can be overcome by co-supplementation with exogenous NO donor. However, NO may potentially counteract anticancer effects of therapy based on arginine deprivation. In this study, we evaluate for the first time the effects of an exogenous NO donor, sodium nitroprusside, on viability and metastatic properties of two human melanoma cell lines SK-MEL-28 and WM793 under arginine-deprived conditions. It was revealed that NO did not rescue melanoma cells from specific effects evoked by arginine deprivation, namely decreased viability and induction of apoptosis, dramatically reduced motility, invasiveness and clonogenic potential. Moreover, sodium nitroprusside co-treatment augmented several of these antineoplastic effects. We report that a combination of NO-donor and arginine deprivation strongly and specifically impaired metastatic behavior of melanoma cells. Thus, sodium nitroprusside can be considered as an adjuvant for the more efficient treatment of malignant melanoma and possibly other tumors with arginine-degrading enzymes.
authors.affiliation: Department of Cell Signaling, Institute of Cell Biology, National Academy of Sciences of Ukraine, 14/16 Drahomanov Str., 79005 Lviv, Ukraine.
authors.forename: Oksana
authors.initials: O
authors.lastname: Mayevska
authors.affiliation: Department of Cell Signaling, Institute of Cell Biology, National Academy of Sciences of Ukraine, 14/16 Drahomanov Str., 79005 Lviv, Ukraine.
authors.forename: Oleh
authors.initials: O
authors.lastname: Chen
authors.affiliation: Department of Cell Signaling, Institute of Cell Biology, National Academy of Sciences of Ukraine, 14/16 Drahomanov Str., 79005 Lviv, Ukraine; Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Str., 02-093 Warsaw, Poland.
authors.forename: Olena
authors.initials: O
authors.lastname: Karatsai
authors.affiliation: Department of Cell Signaling, Institute of Cell Biology, National Academy of Sciences of Ukraine, 14/16 Drahomanov Str., 79005 Lviv, Ukraine.
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Bobak
authors.affiliation: Department of Cell Signaling, Institute of Cell Biology, National Academy of Sciences of Ukraine, 14/16 Drahomanov Str., 79005 Lviv, Ukraine.
authors.forename: Maryna
authors.initials: M
authors.lastname: Barska
authors.affiliation: Department of Cell Signaling, Institute of Cell Biology, National Academy of Sciences of Ukraine, 14/16 Drahomanov Str., 79005 Lviv, Ukraine.
authors.forename: Liliana
authors.initials: L
authors.lastname: Lyniv
authors.affiliation: Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Str., 02-093 Warsaw, Poland.
authors.forename: Iuliia
authors.initials: I
authors.lastname: Pavlyk
authors.affiliation: Department of Cell Signaling, Institute of Cell Biology, National Academy of Sciences of Ukraine, 14/16 Drahomanov Str., 79005 Lviv, Ukraine.
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Rzhepetskyy
authors.affiliation: Department of Cell Signaling, Institute of Cell Biology, National Academy of Sciences of Ukraine, 14/16 Drahomanov Str., 79005 Lviv, Ukraine.
authors.forename: Natalia
authors.initials: N
authors.lastname: Igumentseva
authors.affiliation: Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Str., 02-093 Warsaw, Poland.
authors.forename: Maria Jolanta
authors.initials: MJ
authors.lastname: Redowicz
authors.affiliation: Department of Cell Signaling, Institute of Cell Biology, National Academy of Sciences of Ukraine, 14/16 Drahomanov Str., 79005 Lviv, Ukraine. Electronic address: stasyk@cellbiol.lviv.ua.
authors.forename: Oleh
authors.initials: O
authors.lastname: Stasyk
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001120:Arginine / Q000172:deficiency* / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004359:Drug Therapy, Combination; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000096:biosynthesis; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine
keywords: Arginine deprivation; Cell motility; Melanoma; Nitric oxide; Sodium nitroprusside