Carla Maria Rozzo
Researcher
Area of interest:
Carla Maria Rozzo graduated in Biological Sciences at the University of Cagliari in 1985 and, after some post-doctoral experiences at IIGB-CNR in Naples (1986-1988), at the Scripps Research Institute in La Jolla, California, USA (1986-1991) and at the G. Gaslini Children’s Hospital and Research Institute in Genoa (1991-1994), in November 1994 she became a research scientist at CNR. At present she works at the IRGB-CNR. Her research activity started with basic molecular biology (cloning and characterization of new genes), then focusing on cellular and molecular biology of tumors. Within this field her interests concerned the search for biological modifiers and novel differentiation therapies for neuroectodermal tumors, the mechanisms of cell adhesion and the role of integrins in neuroblastoma cells differentiation and apoptosis. Then she started focusing on molecular biology of malignant melanoma using primary cell lines as a research model for the identification and characterization of molecules (natural or synthetic) as potential broad-spectrum antitumor agents, highlighting the molecular mechanisms underlying their anticancer activity. At present, she participates in the activity of the Sassari Cancer Genetics Unit of CNR, focused on genetic analysis and molecular diagnostics in the oncology field. In particular, her activity involves clinical-translational and basic research, focusing on precision medicine applied to medical oncology. Since 2007, until 2020, she has also overseen the organization of scientific dissemination and orientation activities of the CNR Research Area of Sassari, towards secondary schools.
Most significant publications:
2024
Paola, Peluso; Victor, Mamane; Ylenia, Spissu; Giuseppina, Casu; Alessandro, Dessì; Roberto, Dallocchio; Barbara, Sechi; Giuseppe, Palmieri; Carla., Rozzo
Iodinated 4,4’-Bipyridines with Antiproliferative Activity Against Melanoma Cell Lines Journal Article
In: Chemical Medicinal Chemistry, (e202300662), pp. 1-12, 2024, ISSN: 1860-7187.
@article{,
title = {Iodinated 4,4’-Bipyridines with Antiproliferative Activity Against Melanoma Cell Lines},
author = {Peluso Paola and Mamane Victor and Spissu Ylenia and Casu Giuseppina and Dessì Alessandro and Dallocchio Roberto and Sechi Barbara and Palmieri Giuseppe and Rozzo Carla. },
url = {https://irgb.cnr.it/chemmedchem-2024-peluso-et-al-2024-2/},
doi = {doi.org/10.1002/cmdc.202300662},
issn = {1860-7187},
year = {2024},
date = {2024-03-15},
urldate = {2024-03-15},
journal = {Chemical Medicinal Chemistry},
number = {e202300662},
pages = {1-12},
abstract = {In the last decade, biological processes involving halogen bond (HaB) as a leading interaction attracted great interest. Iodinated 4,4’-bipyridines showed interesting properties as HaB donors in solution and in the solid state. This study represents a proof-of-principle exploration aiming to investigate the effectiveness of new iodinated compounds against melanoma cells. The authors investigated on the inhibition activity exerted by seven halogenated 4,4’-bipyridines on malignant melanoma cell proliferation. The 3,3’,5,5’-tetrachloro-2-iodo-4,4’-bipyridine showed significant antiproliferation activity against the A375 cell line, and lower toxicity on BJ fibroblasts. The results suggested that the antiproliferative activity, at molecular level, may be correlated with the electrophilic properties of iodine. Through in silico studies, the stereoelectronic features of possible sites determining the bioactivity were explored. The obtained results confirmed the high potential of iodinated compounds in designing novel anti-melanoma therapeutics strategies considering the utilization of iodinated 4,4’-bipyridines as templates to design new promising HaB-enabled inhibitors of MM cell proliferation, paving the way for a new perspective in this field.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In the last decade, biological processes involving halogen bond (HaB) as a leading interaction attracted great interest. Iodinated 4,4’-bipyridines showed interesting properties as HaB donors in solution and in the solid state. This study represents a proof-of-principle exploration aiming to investigate the effectiveness of new iodinated compounds against melanoma cells. The authors investigated on the inhibition activity exerted by seven halogenated 4,4’-bipyridines on malignant melanoma cell proliferation. The 3,3’,5,5’-tetrachloro-2-iodo-4,4’-bipyridine showed significant antiproliferation activity against the A375 cell line, and lower toxicity on BJ fibroblasts. The results suggested that the antiproliferative activity, at molecular level, may be correlated with the electrophilic properties of iodine. Through in silico studies, the stereoelectronic features of possible sites determining the bioactivity were explored. The obtained results confirmed the high potential of iodinated compounds in designing novel anti-melanoma therapeutics strategies considering the utilization of iodinated 4,4’-bipyridines as templates to design new promising HaB-enabled inhibitors of MM cell proliferation, paving the way for a new perspective in this field.
2022
Rocchitta, Gaia; Rozzo, Carla; Pisano, Marina; Fabbri, Davide; Dettori, Maria Antonietta; Ruzza, Paolo; Honisch, Claudia; Dallocchio, Roberto; Dessì, Alessandro; Migheli, Rossana; Serra, PierAndrea; Delogu, Giovanna
Inhibitory Effect of Curcumin-Inspired Derivatives on Tyrosinase Activity and Melanogenesis Journal Article
In: Molecules, 27 (7942), pp. 1-24, 2022.
@article{nokey,
title = {Inhibitory Effect of Curcumin-Inspired Derivatives on Tyrosinase Activity and Melanogenesis},
author = {Gaia Rocchitta and Carla Rozzo and Marina Pisano and Davide Fabbri and Maria Antonietta Dettori and
Paolo Ruzza and Claudia Honisch and Roberto Dallocchio and Alessandro Dessì and Rossana Migheli and
PierAndrea Serra and Giovanna Delogu},
url = {https://doi.org/10.3390/molecules27227942
https://irgb.cnr.it/wp-content/uploads/2024/05/Rocchitta-et-al-2022-2.pdf},
doi = {https://doi.org/10.3390/molecules27227942},
year = {2022},
date = {2022-11-16},
urldate = {2022-11-16},
journal = {Molecules},
volume = {27},
number = {7942},
pages = {1-24},
abstract = {Tyrosinase is a well-known copper-containing metalloenzyme typically involved in the synthesis of melanin. Recently, curcumin and several synthetic derivatives have been recognized as tyrosinase inhibitors with interesting anti-melanogenic therapeutic activity. In this study, three curcumin-inspired compounds 1, 6 and 7 were prepared in yields ranging from 60 to 88 % and spectrophotometric, electrochemical, in vitro and in silico analyses were carried out. The viability of PC12 cells, a rat pheochromocytoma derived-cell line, with compounds 1, 6 and 7, showed values around 80% at 5 uM concentration. In cell proliferation assays, compounds 1, 6 and 7 did not show significant toxicity on fibroblasts nor melanoma cells up to 10 uM with viability values over 90%. The inhibition of tyrosinase activity was evaluated both by a UV-Vis spectroscopic method at two different concentrations, 0.2 and 2.0 uM, and by amperometric assay with IC50 for compounds 1, 6 and 7 ranging from 11 to 24 nM. Melanin content assays on human melanoma cells were performed to test the capability of compounds to inhibit melanin biosynthesis. All compounds exerted a decrease in melanin content, with compound 7 being the most effective by showing a melanogenesis inhibition up to four times greater than arbutin at 100 uM. Moreover, the antioxidant activity of the selected inhibitors was evaluated against H2O2 in amperometric experiments, whereby compound 7 was about three times more effective compared to compounds 1 and 6. The tyrosinase X-ray structure of Bacterium megaterium crystal was used to carry out molecular docking studies in the presence of compounds 1, 6 and 7 in comparison with that of kojic acid and arbutin, two conventional tyrosinase inhibitors. Molecular docking of compounds 6 and 7 confirmed the high affinity of these compounds to tyrosinase protein.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Tyrosinase is a well-known copper-containing metalloenzyme typically involved in the synthesis of melanin. Recently, curcumin and several synthetic derivatives have been recognized as tyrosinase inhibitors with interesting anti-melanogenic therapeutic activity. In this study, three curcumin-inspired compounds 1, 6 and 7 were prepared in yields ranging from 60 to 88 % and spectrophotometric, electrochemical, in vitro and in silico analyses were carried out. The viability of PC12 cells, a rat pheochromocytoma derived-cell line, with compounds 1, 6 and 7, showed values around 80% at 5 uM concentration. In cell proliferation assays, compounds 1, 6 and 7 did not show significant toxicity on fibroblasts nor melanoma cells up to 10 uM with viability values over 90%. The inhibition of tyrosinase activity was evaluated both by a UV-Vis spectroscopic method at two different concentrations, 0.2 and 2.0 uM, and by amperometric assay with IC50 for compounds 1, 6 and 7 ranging from 11 to 24 nM. Melanin content assays on human melanoma cells were performed to test the capability of compounds to inhibit melanin biosynthesis. All compounds exerted a decrease in melanin content, with compound 7 being the most effective by showing a melanogenesis inhibition up to four times greater than arbutin at 100 uM. Moreover, the antioxidant activity of the selected inhibitors was evaluated against H2O2 in amperometric experiments, whereby compound 7 was about three times more effective compared to compounds 1 and 6. The tyrosinase X-ray structure of Bacterium megaterium crystal was used to carry out molecular docking studies in the presence of compounds 1, 6 and 7 in comparison with that of kojic acid and arbutin, two conventional tyrosinase inhibitors. Molecular docking of compounds 6 and 7 confirmed the high affinity of these compounds to tyrosinase protein.
Dallocchio, Roberto; Dessì, Alessandro; Sechi, Barbara; Chankvetadze, Bezhan; Cossu, Sergio; Mamane, Victor; Aubert, Emmanuel; Rozzo, Carla; Palmieri, Giuseppe; Spissu, Ylenia; Peluso., Paola
In: Journal of Chromatography Open, 2 (100030), pp. 1-10, 2022, ISSN: 2772-3917.
@article{nokey,
title = {Exploring interaction modes between polysaccharide-based selectors and biologically active 4,4 ′ -bipyridines by experimental and computational analysis. },
author = {Roberto Dallocchio and Alessandro Dessì and Barbara Sechi and Bezhan Chankvetadze and Sergio Cossu and Victor Mamane and Emmanuel Aubert and Carla Rozzo and Giuseppe Palmieri and Ylenia Spissu and Paola Peluso. },
url = {https://irgb.cnr.it/wp-content/uploads/2024/05/Dallocchio-et-al-2022.pdf},
doi = {10.1016/j.jcoa.2022.100030},
issn = {2772-3917},
year = {2022},
date = {2022-01-06},
urldate = {2022-01-06},
journal = {Journal of Chromatography Open},
volume = {2},
number = {100030},
pages = {1-10},
abstract = {In the last few years, chiral 4,4 ′ -bipyridine derivatives have been developed for different applications in catalysis, enantioseparation science, supramolecular and theoretical chemistry by modulating the activity of the molecu- lar system through the introduction of specific substituents in the heteroaromatic scaffold. More recently, the biological activity of 2 ′ -substituted-3,3 ′ ,5,5 ′ -tetrachloro-2-iodo-4,4 ′ -bipyridines has been explored in the field of transthyretin (TTR) fibrillogenesis inhibition, and the anticancer cytotoxicity of some derivatives is currently under systematic investigation. In this frame, the high-performance liquid chromatography (HPLC) enantiosepa- ration of four atropisomeric 2,2 ′ -disubstituted-4,4 ′ -bipyridines (R, R’ = Ar, I), which contain multiple interaction sites, such as hydrogen bonding (HB) donors and acceptors, halogen bond (XB) donors, and 𝜋-extended electronic clouds, was explored by using n -hexane (Hex)/2-propanol (2-PrOH) 90:10 v/v as a mobile phase (MP), and eight chiral columns with coated and immobilized amylose- and cellulose-based selectors. The impact of subtle struc- tural variations of analytes and selectors on their mutual intermolecular interactivity was evaluated in terms of retention ( k ) and selectivity ( 𝛼) factors. On this basis, chromatographic analysis based on systematic screening of analytes and selectors was integrated with electrostatic potential ( V ) analysis and molecular dynamics (MD) sim- ulations as computational techniques. The effect of temperature on retention, selectivity, and enantiomer elution order (EEO) of the analytes with coated and immobilized amylose tris (3,5-dimethylphenylcarbamate) was also considered by comparing the variation of the thermodynamic profile associated with each enantioseparation. Chromatographic responses proved to be strictly dependent on specific regions within the analyte, and functions of different interactions sites of the analytes as the structure of the chiral selector changes were significantly disclosed.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In the last few years, chiral 4,4 ′ -bipyridine derivatives have been developed for different applications in catalysis, enantioseparation science, supramolecular and theoretical chemistry by modulating the activity of the molecu- lar system through the introduction of specific substituents in the heteroaromatic scaffold. More recently, the biological activity of 2 ′ -substituted-3,3 ′ ,5,5 ′ -tetrachloro-2-iodo-4,4 ′ -bipyridines has been explored in the field of transthyretin (TTR) fibrillogenesis inhibition, and the anticancer cytotoxicity of some derivatives is currently under systematic investigation. In this frame, the high-performance liquid chromatography (HPLC) enantiosepa- ration of four atropisomeric 2,2 ′ -disubstituted-4,4 ′ -bipyridines (R, R’ = Ar, I), which contain multiple interaction sites, such as hydrogen bonding (HB) donors and acceptors, halogen bond (XB) donors, and 𝜋-extended electronic clouds, was explored by using n -hexane (Hex)/2-propanol (2-PrOH) 90:10 v/v as a mobile phase (MP), and eight chiral columns with coated and immobilized amylose- and cellulose-based selectors. The impact of subtle struc- tural variations of analytes and selectors on their mutual intermolecular interactivity was evaluated in terms of retention ( k ) and selectivity ( 𝛼) factors. On this basis, chromatographic analysis based on systematic screening of analytes and selectors was integrated with electrostatic potential ( V ) analysis and molecular dynamics (MD) sim- ulations as computational techniques. The effect of temperature on retention, selectivity, and enantiomer elution order (EEO) of the analytes with coated and immobilized amylose tris (3,5-dimethylphenylcarbamate) was also considered by comparing the variation of the thermodynamic profile associated with each enantioseparation. Chromatographic responses proved to be strictly dependent on specific regions within the analyte, and functions of different interactions sites of the analytes as the structure of the chiral selector changes were significantly disclosed.
2021
Palmieri, Giuseppe; Rozzo, Carla Maria; Colombino, Maria; Casula, Milena; Sini, Maria Cristina; Manca, Antonella; Pisano, Marina; Doneddu, Valentina; Paliogiannis, Panagiotis; Cossu., Antonio
In: Frontiers in Oncology, 11 (666624), pp. 1-11, 2021, ISSN: 2234-943X.
@article{nokey,
title = {Are Molecular Alterations Linked to Genetic Instability Worth to Be Included as Biomarkers for Directing or Excluding Melanoma Patients to Immunotherapy? },
author = {Giuseppe Palmieri and Carla Maria Rozzo and Maria Colombino and Milena Casula and Maria Cristina Sini and Antonella Manca and Marina Pisano and Valentina Doneddu and Panagiotis Paliogiannis and Antonio Cossu. },
url = {https://irgb.cnr.it/wp-content/uploads/2024/05/Palmieri-et-al-2021-1.pdf},
doi = {doi: 10.3389/fonc.2021.666624},
issn = {2234-943X},
year = {2021},
date = {2021-05-05},
urldate = {2021-05-05},
journal = {Frontiers in Oncology},
volume = {11},
number = {666624},
pages = {1-11},
abstract = {The improvement of the immunotherapeutic potential in most human cancers, including melanoma, requires the identification of increasingly detailed molecular features underlying the tumor immune responsiveness and acting as disease-associated biomarkers. In recent past years, the complexity of the immune landscape in cancer tissues is being steadily unveiled with a progressive better understanding of the plethora of actors playing in such a scenario, resulting in histopathology diversification, distinct molecular subtypes, and biological heterogeneity. Actually, it is widely recognized that the intracellular patterns of alterations in driver genes and loci may also concur to interfere with the homeostasis of the tumor microenvironment components, deeply affecting the immune response against the tumor. Among others, the different events linked to genetic instability—aneuploidy/somatic copy number alteration (SCNA) or microsatellite instability (MSI)—may exhibit opposite behaviors in terms of immune exclusion or responsiveness.
In this review, we focused on both prevalence and impact of such different types of genetic instability in melanoma in order to evaluate whether their use as biomarkers in an integrated analysis of the molecular profile of such a malignancy may allow defining any potential predictive value for response/resistance to immunotherapy.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The improvement of the immunotherapeutic potential in most human cancers, including melanoma, requires the identification of increasingly detailed molecular features underlying the tumor immune responsiveness and acting as disease-associated biomarkers. In recent past years, the complexity of the immune landscape in cancer tissues is being steadily unveiled with a progressive better understanding of the plethora of actors playing in such a scenario, resulting in histopathology diversification, distinct molecular subtypes, and biological heterogeneity. Actually, it is widely recognized that the intracellular patterns of alterations in driver genes and loci may also concur to interfere with the homeostasis of the tumor microenvironment components, deeply affecting the immune response against the tumor. Among others, the different events linked to genetic instability—aneuploidy/somatic copy number alteration (SCNA) or microsatellite instability (MSI)—may exhibit opposite behaviors in terms of immune exclusion or responsiveness.
In this review, we focused on both prevalence and impact of such different types of genetic instability in melanoma in order to evaluate whether their use as biomarkers in an integrated analysis of the molecular profile of such a malignancy may allow defining any potential predictive value for response/resistance to immunotherapy.
In this review, we focused on both prevalence and impact of such different types of genetic instability in melanoma in order to evaluate whether their use as biomarkers in an integrated analysis of the molecular profile of such a malignancy may allow defining any potential predictive value for response/resistance to immunotherapy.
Pisano, Marina; Dettori, Maria Antonietta; Fabbri, Davide; Delogu, Giovanna; Palmieri, Giuseppe; Rozzo., Carla
Anticancer activity of two novel hydroxylated biphenyl compounds toward malignant melanoma cells. Journal Article
In: International Journal of Molecular Sciences, 22 (5636), pp. 1-18, 2021, ISSN: 1422-0067.
@article{nokey,
title = {Anticancer activity of two novel hydroxylated biphenyl compounds toward malignant melanoma cells.},
author = {Marina Pisano and Maria Antonietta Dettori and Davide Fabbri and Giovanna Delogu and Giuseppe Palmieri and Carla Rozzo. },
url = {https://irgb.cnr.it/wp-content/uploads/2024/05/Pisano-et-al-2021-reprint.pdf},
doi = {10.3390/ijms22115636},
issn = {1422-0067},
year = {2021},
date = {2021-03-26},
urldate = {2021-03-26},
journal = {International Journal of Molecular Sciences},
volume = {22},
number = {5636},
pages = {1-18},
abstract = {Melanoma, the deadliest form of skin cancer, is still one of the most difficult cancers to treat despite recent advances in targeted and immune therapies. About 50% of advanced melanoma do not benefit of such therapies, and novel treatments are requested. Curcumin and its analogs have shown good anticancer properties and are being considered for use in combination with or sequence to recent therapies to improve patient outcomes. Our group previously published the synthesis and anticancer activity characterization of a novel curcumin-related compound against melanoma and neuroblastoma cells (D6). Here, two hydroxylated biphenyl compounds—namely, compounds 11 and 12—were selected among a small collection of previously screened C2-symmetric hydroxylated biphenyls structurally related to D6 and curcumin, showing the best antitumor potentiality against melanoma cells (IC50 values of 1.7 uM 0.5 uM for 11 and 2.0 uM 0.7 uM for 12) and no toxicity of normal fibroblasts up to 32 uM. Their antiproliferative activity was deeply characterized on five melanoma cell lines by performing dose-response and clonal growth inhibition assays, which revealed longlasting and irreversible effects for both compounds. Apoptosis induction was ascertained by the annexin V and TUNEL assays, whereas Western blotting showed caspase activation and PARP cleavage. A cell cycle analysis, following cell treatments with either compound 11 or 12, highlighted an arrest in the G2/M transition. Taking all this evidence together, 11 and 12 were shown to be good candidates as lead compounds to develop new anticancer drugs against malignant melanoma.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Melanoma, the deadliest form of skin cancer, is still one of the most difficult cancers to treat despite recent advances in targeted and immune therapies. About 50% of advanced melanoma do not benefit of such therapies, and novel treatments are requested. Curcumin and its analogs have shown good anticancer properties and are being considered for use in combination with or sequence to recent therapies to improve patient outcomes. Our group previously published the synthesis and anticancer activity characterization of a novel curcumin-related compound against melanoma and neuroblastoma cells (D6). Here, two hydroxylated biphenyl compounds—namely, compounds 11 and 12—were selected among a small collection of previously screened C2-symmetric hydroxylated biphenyls structurally related to D6 and curcumin, showing the best antitumor potentiality against melanoma cells (IC50 values of 1.7 uM 0.5 uM for 11 and 2.0 uM 0.7 uM for 12) and no toxicity of normal fibroblasts up to 32 uM. Their antiproliferative activity was deeply characterized on five melanoma cell lines by performing dose-response and clonal growth inhibition assays, which revealed longlasting and irreversible effects for both compounds. Apoptosis induction was ascertained by the annexin V and TUNEL assays, whereas Western blotting showed caspase activation and PARP cleavage. A cell cycle analysis, following cell treatments with either compound 11 or 12, highlighted an arrest in the G2/M transition. Taking all this evidence together, 11 and 12 were shown to be good candidates as lead compounds to develop new anticancer drugs against malignant melanoma.
Dettori, Maria Antonietta; Fabbri, Davide; Pisano, Marina; Rozzo, Carla; Delogu, Giovanna
In: ChemMedChem, 16 , pp. 1022-1033, 2021.
@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 = {Maria Antonietta Dettori and Davide Fabbri and Marina Pisano and Carla Rozzo and Giovanna Delogu },
url = {https://irgb.cnr.it/wp-content/uploads/2024/05/reprint-1.pdf},
doi = {doi.org/10.1002/cmdc.202000709},
year = {2021},
date = {2021-01-21},
urldate = {2021-01-21},
journal = {ChemMedChem},
volume = {16},
pages = {1022-1033},
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..},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
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..
2020
Colombino, M.; Rozzo, C.; Paliogiannis, P.; Casula, M.; Manca, A.; Doneddu, V.; Fedeli, M. A.; Sini, M. C.; Palomba, G.; Pisano, M.; Ascierto, P. A.; Caracò, C.; Lissia, A.; Cossu, A.; Palmieri, G.
Comparison of BRAF Mutation Screening Strategies in a Large Real-Life Series of Advanced Melanoma Patients Journal Article
In: J Clin Med, 9 (8), 2020.
@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},
urldate = {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.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
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.
2019
Pisano, Marina; Arru, Claudia; Serra, Maria; Galleri, Grazia; Sanna, Daniele; Garribba, Eugenio; Palmieri, Giuseppe; Rozzo, Carla
Antiproliferative activity of vanadium compounds: effects on the major malignant melanoma molecular pathways Journal Article
In: Metallomics, 11 (10), pp. 1687-1699, 2019.
@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}
}
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.
2017
Rozzo, C; Sanna, D; Garribba, E; Serra, M; Cantara, A; Palmieri, G; Pisano, M
Antitumoral effect of vanadium compounds in malignant melanoma cell lines Journal Article
In: J Inorg Biochem, 174 , pp. 14–24, 2017.
@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}
}
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.
2016
Pisano, M.; Palomba, A.; Tanca, A.; Pagnozzi, D.; Uzzau, S.; Addis, M. F.; Dettori, M. A.; Fabbri, D.; Palmieri, G.; Rozzo, C.
Protein expression changes induced in a malignant melanoma cell line by the curcumin analogue compound D6 Journal Article
In: BMC Cancer, 16 , pp. 317, 2016.
@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}
}
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.
2013
Rozzo, C.; Fanciulli, M.; Fraumene, C.; Corrias, A.; Cubeddu, T.; Sassu, I.; Cossu, S.; Nieddu, V.; Galleri, G.; Azara, E.; Dettori, M. A.; Fabbri, D.; Palmieri, G.; Pisano, M.
Molecular changes induced by the curcumin analogue D6 in human melanoma cells Journal Article
In: Mol Cancer, 12 , pp. 37, 2013.
@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.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
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.
- Traversa la Crucca, 3 – Regione Baldinca, Sassari
- 079 2841227
ORCID ID: https://orcid.org/0000-0001-6581-2227