Carla Maria Rozzo

@article{pmid33274847,

title = {Synthesis of Hydroxylated Biphenyls Derivatives Bearing an α,β-Unsaturated Ketone as Lead Structure for the Development of New Drug Candidates Against Malignant Melanoma},

author = {Dettori, M. A. and Fabbri, D. and Pisano, M. and Rozzo, C. and Delogu, G.},

year  = {2020},

date = {2020-12-01},

journal = {ChemMedChem},

abstract = {A small collection of C 2 -symmetry hydroxylated biphenyls derivatives featured with a α,β-unsaturated ketone as lead structure was prepared and the capability of such compounds to act as antiproliferative agents against four human malignant melanoma cell lines was assayed. The prodrug approach was applied in order to improve delivery of compounds into the cell by modulation of the phenolic-OH protective group. The hydroxylated biphenyl structure bearing an α,β-unsaturated ketone and a phenolic- O -prenylated chain would facilitated the delivery of the molecule and interactions with the biological targets. Four compounds showed antiproliferative activity resulting in IC 50 value in the range 1.2 - 2.8 µM..},

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tppubtype = {article}

}

@article{pmid32751423,

title = {Comparison of BRAF Mutation Screening Strategies in a Large Real-Life Series of Advanced Melanoma Patients},

author = {Colombino, M. and Rozzo, C. and Paliogiannis, P. and Casula, M. and Manca, A. and Doneddu, V. and Fedeli, M. A. and Sini, M. C. and Palomba, G. and Pisano, M. and Ascierto, P. A. and Caracò, C. and Lissia, A. and Cossu, A. and Palmieri, G.},

year  = {2020},

date = {2020-07-01},

journal = {J Clin Med},

volume = {9},

number = {8},

abstract = {Malignant melanoma (MM) is one of the deadliest skin cancers. BRAF mutation status plays a predominant role in the management of MM patients. The aim of this study was to compare BRAF mutational testing performed by conventional nucleotide sequencing approaches with either real-time polymerase chain reaction (rtPCR) or next-generation sequencing (NGS) assays in a real-life, hospital-based series of advanced MM patients. Consecutive patients with AJCC (American Joint Committee on Cancer) stage IIIC and IV MM from Sardinia, Italy, who were referred for molecular testing, were enrolled into the study. Initial screening was performed to assess the mutational status of the BRAF and NRAS genes, using the conventional methodologies recognized by the nationwide guidelines, at the time of the molecular classification, required by clinicians: at the beginning, Sanger-based sequencing (SS) and, after, pyrosequencing. The present study was then focused on BRAF mutation detecting approaches only. BRAF wild-type cases with available tissue and adequate DNA were further tested with rtPCR (Idyllaâ„¢) and NGS assays. Globally, 319 patients were included in the study; pathogenic BRAF mutations were found in 144 (45.1%) cases examined with initial screening. The rtPCR detected 11 (16.2%) and 3 (4.8%) additional BRAF mutations after SS and pyrosequencing, respectively. NGS detected one additional BRAF-mutated case (2.1%) among 48 wild-type cases previously tested with pyrosequencing and rtPCR. Our study evidenced that rtPCR and NGS were able to detect additional BRAF mutant cases in comparison with conventional sequencing methods; therefore, we argue for the preferential utilization of the aforementioned assays (NGS and rtPCR) in clinical practice, to eradicate false-negative cases and improve the accuracy of BRAF detection.},

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pubstate = {published},

tppubtype = {article}

}

@article{pmid31490510,

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

author = {Pisano, M. and Arru, C. and Serra, M. and Galleri, G. and Sanna, D. and Garribba, E. and Palmieri, G. and Rozzo, C.},

year  = {2019},

date = {2019-01-01},

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.},

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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{pmid27192978,

title = {Protein expression changes induced in a malignant melanoma cell line by the curcumin analogue compound D6},

author = {Pisano, M. and Palomba, A. and Tanca, A. and Pagnozzi, D. and Uzzau, S. and Addis, M. F. and Dettori, M. A. and Fabbri, D. and Palmieri, G. and Rozzo, C.},

year  = {2016},

date = {2016-01-01},

journal = {BMC Cancer},

volume = {16},

pages = {317},

abstract = {We have previously demonstrated that the hydroxylated biphenyl compound D6 (3E,3É)-4,4'-(5,5',6,6'-tetramethoxy-[1,1'-biphenyl]-3,3'-diyl)bis(but-3-en-2-one), a structural analogue of curcumin, exerts a strong antitumor activity on melanoma cells both in vitro and in vivo. Although the mechanism of action of D6 is yet to be clarified, this compound is thought to inhibit cancer cell growth by arresting the cell cycle in G2/M phase, and to induce apoptosis through the mitochondrial intrinsic pathway. To investigate the changes in protein expression induced by exposure of melanoma cells to D6, a differential proteomic study was carried out on D6-treated and untreated primary melanoma LB24Dagi cells. Proteins were fractionated by SDS-PAGE and subjected to in gel digestion. The peptide mixtures were analyzed by liquid chromatography coupled with tandem mass spectrometry. Proteins were identified and quantified using database search and spectral counting. Proteomic data were finally uploaded into the Ingenuity Pathway Analysis software to find significantly modulated networks and pathways. Analysis of the differentially expressed protein profiles revealed the activation of a strong cellular stress response, with overexpression of several HSPs and stimulation of ubiquitin-proteasome pathways. These were accompanied by a decrease of protein synthesis, evidenced by downregulation of proteins involved in mRNA processing and translation. These findings are consistent with our previous results on gene expression profiling in melanoma cells treated with D6. Our findings confirm that the curcumin analogue D6 triggers a strong stress response in melanoma cells, turning down majority of cell functions and finally driving cells to apoptosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23642048,

title = {Molecular changes induced by the curcumin analogue D6 in human melanoma cells},

author = {Rozzo, C. and Fanciulli, M. and Fraumene, C. and Corrias, A. and Cubeddu, T. and Sassu, I. and Cossu, S. and Nieddu, V. and Galleri, G. and Azara, E. and Dettori, M. A. and Fabbri, D. and Palmieri, G. and Pisano, M.},

year  = {2013},

date = {2013-05-01},

journal = {Mol Cancer},

volume = {12},

pages = {37},

abstract = {In a previous report, we described the in vitro and in vivo antiproliferative and proapoptotic activity of a hydroxylated biphenyl (D6), a structural analogue of curcumin, on malignant melanoma and neuroblastoma tumours. In this paper, we investigated the molecular changes induced by such a compound, underlying cell growth arrest and apoptosis in melanoma cells. To shed light on the mechanisms of action of D6, we firstly demonstrated its quick cellular uptake and subsequent block of cell cycle in G2/M phase transition. A gene expression profile analysis of D6-treated melanoma cells and fibroblasts was then carried out on high density microarrays, to assess gene expression changes induced by this compound. The expression profile study evidenced both an induction of stress response pathways and a modulation of cell growth regulation mechanisms. In particular, our data suggest that the antiproliferative and proapoptotic activities of D6 in melanoma could be partially driven by up-regulation of the p53 signalling pathways as well as by down-regulation of the PI3K/Akt and NF-kB pathways. Modulation of gene expression due to D6 treatment was verified by western blot analysis for single proteins of interest, confirming the results from the gene expression profile analysis. Our findings contribute to the understanding of the mechanisms of action of D6, through a comprehensive description of the molecular changes induced by this compound at the gene expression level, in agreement with the previously reported anti-tumour effects on melanoma cells.},

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pubstate = {published},

tppubtype = {article}

}