Maria Serra

@article{pmid31490510,

title = {Antiproliferative activity of vanadium compounds: effects on the major malignant melanoma molecular pathways},

author = {Marina Pisano and Claudia Arru and Maria Serra and Grazia Galleri and Daniele Sanna and Eugenio Garribba and Giuseppe Palmieri and Carla Rozzo },

url = {https://irgb.cnr.it/wp-content/uploads/2024/05/Pisano-et-al-2019-reprint.pdf},

year  = {2019},

date = {2019-08-21},

urldate = {2019-08-21},

journal = {Metallomics},

volume = {11},

number = {10},

pages = {1687-1699},

abstract = {Malignant melanoma (MM) is the most fatal skin cancer, whose incidence has critically increased in the last decades. Recent molecular therapies are giving excellent results in the remission of melanoma but often they induce drug resistance in patients limiting their therapeutic efficacy. The search for new compounds able to overcome drug resistance is therefore essential. Vanadium has recently been cited for its anticancer properties against several tumors, but only a few data regard its effect against MM. In a previous work we demonstrated the anticancer activity of four different vanadium species towards MM cell lines. The inorganic anion vanadate(v) (VN) and the oxidovanadium(iv) complex [VO(dhp)2] (VS2), where dhp is 1,2-dimethyl-3-hydroxy-4(1H)-pyridinonate, showed IC50 values of 4.7 and 2.6 μM, respectively, against the A375 MM cell line, causing apoptosis and cell cycle arrest. Here we demonstrate the involvement of Reactive Oxygen Species (ROS) production in the pro-apoptotic effect of these two V species and evaluate the activation of different cell cycle regulators, to investigate the molecular mechanisms involved in their antitumor activity. We establish that VN and VS2 treatments reduce the phosphorylation of extracellular-signal regulated kinase (ERK) by about 80%, causing the deactivation of the mitogen activated protein kinase (MAPK) pathway in A375 cells. VN and VS2 also induce dephosphorylation of the retinoblastoma protein (Rb) (VN 100% and VS2 90%), together with a pronounced increase of cyclin-dependent kinase inhibitor 1 p21 (p21Cip1) protein expression up to 1800%. Taken together, our results confirm the antitumor properties of vanadium against melanoma cells, highlighting its ability to induce apoptosis through generation of ROS and cell cycle arrest by counteracting MAPK pathway activation and strongly inducing p21Cip1 expression and Rb hypo-phosphorylation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28872590,

title = {Synthesis of Nitric Oxide Donors Derived from Piloty's Acid and Study of Their Effects on Dopamine Secretion from PC12 Cells},

author = {Daniele Sanna and Gaia Rocchitta and Maria Serra and Marcello Abbondio and Pier Andrea Serra and Rossana Migheli and Lidia De Luca and Eugenio Garribba and Andrea Porcheddu},

doi = {10.3390/ph10030074},

issn = {1424-8247},

year  = {2017},

date = {2017-05-10},

journal = {Pharmaceuticals (Basel)},

volume = {10},

number = {3},

abstract = {This study investigated the mechanisms and kinetics of nitric oxide (NO) generation by derivatives of Piloty's acid (NO-donors) under physiological conditions. In order to qualitatively and quantitatively measure NO release, electron paramagnetic resonance (EPR) was carried out with NO spin trapping. In addition, voltammetric techniques, including cyclic voltammetry and constant potential amperometry, were used to confirm NO release from Piloty's acid and its derivatives. The resulting data showed that Piloty's acid derivatives are able to release NO under physiological conditions. In particular, electron-withdrawing substituents favoured NO generation, while electron-donor groups reduced NO generation. In vitro microdialysis, performed on PC12 cell cultures, was used to evaluate the dynamical secretion of dopamine induced by the Piloty's acid derivatives. Although all the studied molecules were able to induce DA secretion from PC12, only those with a slow release of NO have not determined an autoxidation of DA itself. These results confirm that the time-course of NO-donors decomposition and the amount of NO released play a key role in dopamine secretion and auto-oxidation. This information could drive the synthesis or the selection of compounds to use as potential drugs for the therapy of Parkinson's disease (PD).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28499214,

title = {Speciation of potential anti-diabetic vanadium complexes in real serum samples},

author = {Daniele Sanna and Valeria Ugone and Maria Serra and Eugenio Garribba},

doi = {10.1016/j.jinorgbio.2017.04.023},

issn = {1873-3344},

year  = {2017},

date = {2017-05-02},

urldate = {2017-05-02},

journal = {J Inorg Biochem},

volume = {173},

pages = {52--65},

abstract = {In this work the speciation in real serum samples of five VO complexes with potential application in the therapy of diabetes was studied through EPR spectroscopy as a function of V concentration (45.4, 90.9 and 454.5μM) and time (0-180min). [VO(dhp)], [VO(ma)], [VO(acac)], [VO(pic)(HO)], and [VO(mepic)], where Hdhp indicates 1,2-dimethyl-3-hydroxy-4(1H)-pyridinone, Hma maltol, Hacac acetylacetone, Hpic picolinic acid, and Hmepic 6-methylpicolinic acid, were examined. The distribution of VO among the serum bioligands was calculated from the thermodynamic stability constants in the literature and compared with the experimental results. EPR results, which confirm the prediction, depend on the strength of the ligand L and geometry assumed by the bis-chelated species at physiological pH, cis-octahedral or square pyramidal. With dhp, the strongest chelator, the system is dominated by [VO(dhp)] and/or cis-VO(dhp)(Protein); with intermediate strength chelators, i.e. maltolate, acetylacetonate and picolinate, by cis-VO(ma)(Protein), [VO(acac)] or [VO(pic)(citrH)]/[VO(pic)(lactH)] (citr=citrate and lact=lactate) when the V concentration overcomes 100-200μM and by (VO)(hTf)/(VO)(hTf) when concentration is lower than 100μM; with the weakest chelator, 6-methylpicolinate, (VO)(hTf)/(VO)(hTf), (VO)(HSA) (hTf = human serum transferrin and HSA = human serum albumin), and VO(mepic)(Protein)(OH) are the major species at concentration higher than 100-200μM, whereas hydrolytic processes are observed for lower concentrations. For [VO(dhp)], [VO(ma)], [VO(acac)] and [VO(pic)(HO)], the EPR spectra remain unaltered with elapsing time, while for mepic they change significantly because the hydrolyzed VO species are complexed by the serum bioligands, in particular by lactate. The rate of oxidation in the serum is [VO(dhp)]>[VO(ma)]>[VO(acac)] and reflects the order of E values.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28558258,

title = {Antitumoral effect of vanadium compounds in malignant melanoma cell lines},

author = {C Rozzo and D Sanna and E Garribba and M Serra and A Cantara and G Palmieri and M Pisano},

year  = {2017},

date = {2017-01-01},

journal = {J Inorg Biochem},

volume = {174},

pages = {14--24},

abstract = {In this study we evaluated the anticancer activity against malignant melanoma (MM) of four different vanadium species: the inorganic anion vanadate(V) (indicated with VN), and three oxidovanadium(IV) complexes, [VIVO(dhp)2] where dhp- is the anion 1,2-dimethyl-3-hydroxy-4(1H)-pyridinonate (indicated with VS2), [VIVO(mpp)2] where mpp- is 1-methyl-3-hydroxy-4(1H)-pyridinonate (indicated with VS3), and [VIVO(ppp)2] where ppp- is 1-phenyl-2-methyl-3-hydroxy-4(1H)-pyridinonate (indicated with VS4). The antitumor effects of these compounds were studied against two different MM cell lines (A375 and CN-mel) and a fibroblast cell line (BJ) as normal control. All tested V compounds exert antiproliferative activity on MM cells in a dose dependent manner (IC50 ranges from 2.4μM up to 14μM) being A375 the most sensitive cell line. VN and VS2 were the two most active compounds against A375 (IC50 of 4.7 and 2.6μM, respectively), causing apoptosis and cell cycle block. The experimental data indicate that the cell cycle arrest occurs at different phases for the two V species analyzed (G2 checkpoint for VN and G0/G1 for VS2), showing the importance of the chemical form in determining their mechanism of action. These results add more insights into the landscape of vanadium versatility in biological systems and into its role as a potential cancer therapeutic agent.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27121101,

title = {Biorelevant reactions of the potential anti-tumor agent vanadocene dichloride},

author = {Daniele Sanna and Maria Serra and Valeria Ugone and Laura Manca and Monica Pirastru and Péter Buglyó and Linda Bíró and Giovanni Micera and Eugenio Garribba},

doi = {10.1039/c6mt00002a},

issn = {1756-591X},

year  = {2016},

date = {2016-04-27},

journal = {Metallomics},

volume = {8},

number = {5},

pages = {532--541},

abstract = {The interaction of the potential anti-tumor agent vanadocene dichloride ([Cp2VCl2] or VDC) with some relevant bioligands of the cytosol such as proteins (Hb), amino acids (glycine and histidine), NADH derivatives (NADH, NADPH, NAD(+) and NADP(+)), reductants (GSH and ascorbic acid), phosphates (HPO4(2-), P2O7(4-), cAMP, AMP, ADP and ATP) and carboxylate derivatives (lactate) and its uptake by red blood cells were studied. The results indicated that [Cp2VCl2] transforms at physiological pH into [Cp2V(OH)2] and that only HPO4(2-), P2O7(4-), lactate, ATP and ADP form mixed species with the [Cp2V](2+) moiety replacing the two hydroxide ions. EPR and electronic absorption spectroscopy, agarose gel electrophoresis and spin trapping measurements allow excluding any direct interaction and/or intercalation with DNA and the formation of reactive oxygen species (ROS) in Fenton-like reactions. Uptake experiments by erythrocytes suggested that VDC crosses the membrane and enters inside the cells, whereas 'bare' V(IV) transforms into V(IV)O species with loss of the two cyclopentadienyl rings. This transformation in the cellular environment could be related to the mechanism of action of VDC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid26281973,

title = {Behavior of the potential antitumor V(IV)O complexes formed by flavonoid ligands. 2. Characterization of sulfonate derivatives of quercetin and morin, interaction with the bioligands of the plasma and preliminary biotransformation studies},

author = {Daniele Sanna and Valeria Ugone and Luisa Pisano and Maria Serra and Giovanni Micera and Eugenio Garribba},

doi = {10.1016/j.jinorgbio.2015.07.018},

issn = {1873-3344},

year  = {2015},

date = {2015-12-21},

journal = {J Inorg Biochem},

volume = {153},

pages = {167--177},

abstract = {The biotransformation in the plasma and red blood cells of two potential antitumor V(IV)O complexes formed by flavonoid ligands (quercetin or que and morin or mor) and their sulfonic derivatives (quercetin-5'-sulfonic acid or que(S) and morin-5'-sulfonic acid or mor(S)) was studied by spectroscopic (EPR, Electron Paramagnetic Resonance) and computational (DFT, Density Functional Theory) methods. Que and que(S) form with V(IV)O stable complexes, and in the systems with apo-transferrin (apo-hTf) and albumin (HSA) VO(que)2 and VO(que(S))2 remain unchanged. VO(mor)2 and VO(mor(S))2 undergo displacement reactions to give the partial formation of (VO)x(HSA) and (VO)(apo-hTf)/(VO)2(apo-hTf); moreover, mor(S) forms with apo-transferrin and albumin mixed species VO-mor(S)-apo-hTf and VO-mor(S)-HSA. In the systems with apo-hTf and HSA anisotropic EPR spectra at room temperature are detected in which the protein is not directly coordinated to V(IV)O(2+) ion. This is explained assuming that the bis-chelated complexes interact strongly with the proteins through a network of hydrogen bonds with the polar groups present on the protein surface. It is suggested that this "indirect" transport of V(IV)O species could be common to all the species containing ligands which can interact with the blood proteins. Uptake experiments by red blood cells were also carried out, using vanadium concentration of 5.0×10(-4)M and incubation time in the range 0-160min. VO(que)2/VO(que(S))2 and VO(mor)2/VO(mor(S))2 cross the erythrocytes membrane and in the cytosol VO(que)2/VO(que(S))2 do not transform, whereas VO(mor)2/VO(mor(S))2 give the partial formation of mixed species with hemoglobin (Hb) and other V(IV)O complexes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid25601642,

title = {Characterization and biotransformation in the plasma and red blood cells of V(IV)O(2+) complexes formed by ceftriaxone},

author = {Daniele Sanna and Davide Fabbri and Maria Serra and Péter Buglyó and Linda Bíró and Valeria Ugone and Giovanni Micera and Eugenio Garribba},

doi = {10.1016/j.jinorgbio.2014.12.021},

issn = {1873-3344},

year  = {2015},

date = {2015-06-23},

journal = {J Inorg Biochem},

volume = {147},

pages = {71--84},

abstract = {The coordination mode and geometry in aqueous solution of oxidovanadium(IV) complexes formed by a third-generation cephalosporin, ceftriaxone (H3cef), were studied by spectroscopic (EPR, electron paramagnetic resonance), pH-potentiometric and computational (DFT, density functional theory) methods. The behavior of the model systems containing 6-hydroxy-2-methyl-3-thioxo-3,4-dihydro-1,2,4-triazine-5(2H)-one (H2hmtdt) and 3-benzylthio-6-hydroxy-2-methyl-1,2,4-triazine-5(2H)-one (Hbhmt) was examined for comparison. The stability of the tautomers of ceftriaxone and 6-hydroxy-2-methyl-3-thioxo-3,4-dihydro-1,2,4-triazine-5(2H)-one in the neutral, mono- and bi-anionic form was calculated by DFT methods, both in the gas phase and in aqueous solution, and the electron density on the oxygen atoms of the hydroxytriazinone ring was related to the pKa of the ligands. The data demonstrate that ceftriaxone coordinates V(IV)O(2+) forming mono- and bis-chelated complexes with (Oket, O(-)) donor set and formation of five-membered chelate rings. The geometry of the bis-chelated complex, cis-[VO(Hcef)2(H2O)](2-), is cis-octahedral and this species can deprotonate, around physiological pH, to form the corresponding mono-hydroxido cis-[VO(Hcef)2(OH)](3-). The interaction of cis-[VO(Hcef)2(H2O)](2-) with apo-transferrin (apo-hTf) was studied and the results suggest that V(IV)O(2+) distributes between (VO)apo-hTf/(VO)2apo-hTf and cis-[VO(Hcef)2(H2O)](2-), whereas mixed complexes are not formed for charge and steric effects. The interaction of cis-[VO(Hcef)2(H2O)](2-) with red blood cells shows that ceftriaxone helps V(IV)O(2+) ion to cross the erythrocyte membrane. Inside the cell cis-[VO(Hcef)2(H2O)](2-) decomposes and the same species formed by inorganic V(IV)O(2+) are observed. The relationship between the biotransformation in the plasma and red blood cells and the potential pharmacological activity of V(IV)O(2+) species of ceftriaxone is finally discussed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid24437949,

title = {Interaction of antidiabetic vanadium compounds with hemoglobin and red blood cells and their distribution between plasma and erythrocytes},

author = {Daniele Sanna and Maria Serra and Giovanni Micera and Eugenio Garribba},

doi = {10.1021/ic402366x},

issn = {1520-510X},

year  = {2014},

date = {2014-05-21},

journal = {Inorg Chem},

volume = {53},

number = {3},

pages = {1449--1464},

abstract = {The interaction of V(IV)O(2+) ion with hemoglobin (Hb) was studied with the combined application of spectroscopic (EPR), spectrophotometric (UV-vis), and computational (DFT methods) techniques. Binding of Hb to V(IV)O(2+) in vitro was proved, and three unspecific sites (named α, β, and γ) were characterized, with the probable coordination of His-N, Asp-O(-), and Glu-O(-) donors. The value of log β for (VO)Hb is 10.4, significantly lower than for human serum apo-transferrin (hTf). In the systems with V(IV)O potential antidiabetic compounds, mixed species cis-VOL2(Hb) (L = maltolate (ma), 1,2-dimethyl-3-hydroxy-4(1H)-pyridinonate (dhp)) are observed with equatorial binding of an accessible His residue, whereas no ternary complexes are observed with acetylacetonate (acac). The experiments of uptake of [VO(ma)2], [VO(dhp)2], and [VO(acac)2] by red blood cells indicate that the neutral compounds penetrate the erythrocyte membrane through passive diffusion, and percent amounts higher than 50% are found in the intracellular medium. The biotransformation of [VO(ma)2], [VO(dhp)2], and [VO(acac)2] inside the red blood cells was proved. [VO(dhp)2] transforms quantitatively in cis-VO(dhp)2(Hb), [VO(ma)2] in cis-VO(ma)2(Hb), and cis-VO(ma)2(Cys-S(-)), with the equatorial coordination of a thiolate-S(-) of GSH or of a membrane protein, and [VO(acac)2] in the binary species (VO)xHb and two V(IV)O complexes with formulation VO(L(1),L(2)) and VO(L(3),L(4)), where L(1), L(2), L(3), and L(4) are red blood cell bioligands. The results indicate that, in the studies on the transport of a potential pharmacologically active V species, the interaction with red blood cells and Hb cannot be neglected, that a distribution between the erythrocytes and plasma is achieved, and that these processes can significantly influence the effectiveness of a V drug.},

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pubstate = {published},

tppubtype = {article}

}