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Article ; Online: Dual Function Molecules and Processes in Cell Fate Decision

Sonia Emanuele / Michela Giuliano

International Journal of Molecular Sciences, Vol 21, Iss 9601, p

A Preface to the Special Issue

2020 Volume 9601

Abstract: A lot of water has passed under the bridge since 1999, when C.J. Jeffery stated in a pioneering review that “the idea of one gene-one protein-one function has become too simple” [.] ...

Abstract	A lot of water has passed under the bridge since 1999, when C.J. Jeffery stated in a pioneering review that “the idea of one gene-one protein-one function has become too simple” [.]
Keywords	n/a ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Hypertrophy and ER Stress Induced by Palmitate Are Counteracted by Mango Peel and Seed Extracts in 3T3-L1 Adipocytes

Giovanni Pratelli / Diana Di Liberto / Daniela Carlisi / Sonia Emanuele / Michela Giuliano / Antonietta Notaro / Anna De Blasio / Giuseppe Calvaruso / Antonella D’Anneo / Marianna Lauricella

International Journal of Molecular Sciences, Vol 24, Iss 5419, p

2023 Volume 5419

Abstract: A diet rich in saturated fatty acids (FAs) has been correlated with metabolic dysfunction and ROS increase in the adipose tissue of obese subjects. Thus, reducing hypertrophy and oxidative stress in adipose tissue can represent a strategy to counteract ... ...

Abstract	A diet rich in saturated fatty acids (FAs) has been correlated with metabolic dysfunction and ROS increase in the adipose tissue of obese subjects. Thus, reducing hypertrophy and oxidative stress in adipose tissue can represent a strategy to counteract obesity and obesity-related diseases. In this context, the present study showed how the peel and seed extracts of mango ( Mangifera indica L .) reduced lipotoxicity induced by high doses of sodium palmitate (PA) in differentiated 3T3-L1 adipocytes. Mango peel (MPE) and mango seed (MSE) extracts significantly lowered PA-induced fat accumulation by reducing lipid droplet (LDs) and triacylglycerol (TAGs) content in adipocytes. We showed that MPE and MSE activated hormone-sensitive lipase, the key enzyme of TAG degradation. In addition, mango extracts down-regulated the adipogenic transcription factor PPARγ as well as activated AMPK with the consequent inhibition of acetyl-CoA-carboxylase (ACC). Notably, PA increased endoplasmic reticulum (ER) stress markers GRP78, PERK and CHOP, as well as enhanced the reactive oxygen species (ROS) content in adipocytes. These effects were accompanied by a reduction in cell viability and the induction of apoptosis. Interestingly, MPE and MSE counteracted PA-induced lipotoxicity by reducing ER stress markers and ROS production. In addition, MPE and MSE increased the level of the anti-oxidant transcription factor Nrf2 and its targets MnSOD and HO-1. Collectively, these results suggest that the intake of mango extract-enriched foods in association with a correct lifestyle could exert beneficial effects to counteract obesity.
Keywords	mango peel extracts ; mango seed extracts ; saturated fatty acids ; 3T3-L1 adipocytes ; ER stress ; AMPK ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	571
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Oncogenic BRAF and p53 Interplay in Melanoma Cells and the Effects of the HDAC Inhibitor ITF2357 (Givinostat)

Adriana Celesia / Marzia Franzò / Diana Di Liberto / Marianna Lauricella / Daniela Carlisi / Antonella D’Anneo / Antonietta Notaro / Mario Allegra / Michela Giuliano / Sonia Emanuele

International Journal of Molecular Sciences, Vol 24, Iss 9148, p

2023 Volume 9148

Abstract: Oncogenic BRAF mutations have been widely described in melanomas and promote tumour progression and chemoresistance. We previously provided evidence that the HDAC inhibitor ITF2357 (Givinostat) targets oncogenic BRAF in SK-MEL-28 and A375 melanoma cells. ...

Abstract	Oncogenic BRAF mutations have been widely described in melanomas and promote tumour progression and chemoresistance. We previously provided evidence that the HDAC inhibitor ITF2357 (Givinostat) targets oncogenic BRAF in SK-MEL-28 and A375 melanoma cells. Here, we show that oncogenic BRAF localises to the nucleus of these cells, and the compound decreases BRAF levels in both the nuclear and cytosolic compartments. Although mutations in the tumour suppressor p53 gene are not equally frequent in melanomas compared to BRAF, the functional impairment of the p53 pathway may also contribute to melanoma development and aggressiveness. To understand whether oncogenic BRAF and p53 may cooperate, a possible interplay was considered in the two cell lines displaying a different p53 status, being p53 mutated into an oncogenic form in SK-MEL-28 and wild-type in A375 cells. Immunoprecipitation revealed that BRAF seems to preferentially interact with oncogenic p53. Interestingly, ITF2357 not only reduced BRAF levels but also oncogenic p53 levels in SK-MEL-28 cells. ITF2357 also targeted BRAF in A375 cells but not wild-type p53, which increased, most likely favouring apoptosis. Silencing experiments confirmed that the response to ITF2357 in BRAF-mutated cells depends on p53 status, thus providing a rationale for melanoma-targeted therapy.
Keywords	HDAC inhibitor ; ITF2357 ; BRAF ; melanoma ; p53 ; apoptosis ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	572
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: MCL1 Inhibition Overcomes the Aggressiveness Features of Triple-Negative Breast Cancer MDA-MB-231 Cells

Giovanni Pratelli / Daniela Carlisi / Diana Di Liberto / Antonietta Notaro / Michela Giuliano / Antonella D’Anneo / Marianna Lauricella / Sonia Emanuele / Giuseppe Calvaruso / Anna De Blasio

International Journal of Molecular Sciences, Vol 24, Iss 11149, p

2023 Volume 11149

Abstract: Triple-Negative Breast Cancer (TNBC) is a particularly aggressive subtype among breast cancers (BCs), characterized by anoikis resistance, high invasiveness, and metastatic potential as well as Epithelial–Mesenchymal Transition (EMT) and stemness ... ...

Abstract	Triple-Negative Breast Cancer (TNBC) is a particularly aggressive subtype among breast cancers (BCs), characterized by anoikis resistance, high invasiveness, and metastatic potential as well as Epithelial–Mesenchymal Transition (EMT) and stemness features. In the last few years, our research focused on the function of MCL1, an antiapoptotic protein frequently deregulated in TNBC. Here, we demonstrate that MCL1 inhibition by A-1210477, a specific BH3-mimetic, promotes anoikis/apoptosis in the MDA-MB-231 cell line, as shown via an increase in proapoptotic markers and caspase activation. Our evidence also shows A-1210477 effects on Focal Adhesions (FAs) impairing the integrin trim and survival signaling pathways, such as FAK, AKT, ERK, NF-κB, and GSK3β-inducing anoikis, thus suggesting a putative role of MCL1 in regulation of FA dynamics. Interestingly, in accordance with these results, we observed a reduction in migratory and invasiveness capabilities as confirmed by a decrease in metalloproteinases (MMPs) levels following A-1210477 treatment. Moreover, MCL1 inhibition promotes a reduction in EMT characteristics as demonstrated by the downregulation of Vimentin, MUC1, DNMT1, and a surprising re-expression of E-Cadherin, suggesting a possible mesenchymal-like phenotype reversion. In addition, we also observed the downregulation of stemness makers such as OCT3/4 , SOX2 , NANOG , as well as CD133, EpCAM, and CD49f. Our findings support the idea that MCL1 inhibition in MDA-MB-231 could be crucial to reduce anoikis resistance, aggressiveness, and metastatic potential and to minimize EMT and stemness features that distinguish TNBC.
Keywords	TNBC ; anoikis resistance ; EMT ; cancer stem cells ; MCL1 ; BH3-mimetic ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Good and Bad of Nrf2

Sonia Emanuele / Adriana Celesia / Antonella D’Anneo / Marianna Lauricella / Daniela Carlisi / Anna De Blasio / Michela Giuliano

International Journal of Molecular Sciences, Vol 22, Iss 7963, p

An Update in Cancer and New Perspectives in COVID-19

2021 Volume 7963

Abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) is a well-known transcription factor best recognised as one of the main regulators of the oxidative stress response. Beyond playing a crucial role in cell defence by transactivating cytoprotective genes ... ...

Abstract	Nuclear factor erythroid 2-related factor 2 (Nrf2) is a well-known transcription factor best recognised as one of the main regulators of the oxidative stress response. Beyond playing a crucial role in cell defence by transactivating cytoprotective genes encoding antioxidant and detoxifying enzymes, Nrf2 is also implicated in a wide network regulating anti-inflammatory response and metabolic reprogramming. Such a broad spectrum of actions renders the factor a key regulator of cell fate and a strategic player in the control of cell transformation and response to viral infections. The Nrf2 protective roles in normal cells account for its anti-tumour and anti-viral functions. However, Nrf2 overstimulation often occurs in tumour cells and a complex correlation of Nrf2 with cancer initiation and progression has been widely described. Therefore, if on one hand, Nrf2 has a dual role in cancer, on the other hand, the factor seems to display a univocal function in preventing inflammation and cytokine storm that occur under viral infections, specifically in coronavirus disease 19 (COVID-19). In such a variegate context, the present review aims to dissect the roles of Nrf2 in both cancer and COVID-19, two widespread diseases that represent a cause of major concern today. In particular, the review describes the molecular aspects of Nrf2 signalling in both pathological situations and the most recent findings about the advantages of Nrf2 inhibition or activation as possible strategies for cancer and COVID-19 treatment respectively.
Keywords	Nrf2 ; oxidative stress ; cell death ; cancer ; COVID-19 ; NF-κB ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Beneficial Effects of Essential Oils in Anti-Obesity Treatment

Anna De Blasio / Antonella D’Anneo / Marianna Lauricella / Sonia Emanuele / Michela Giuliano / Giovanni Pratelli / Giuseppe Calvaruso / Daniela Carlisi

International Journal of Molecular Sciences, Vol 22, Iss 11832, p

2021 Volume 11832

Abstract: Obesity is a complex disease caused by an excessive amount of body fat. Obesity is a medical problem and represents an important risk factor for the development of serious diseases such as insulin resistance, type 2 diabetes, cardiovascular disease, and ... ...

Abstract	Obesity is a complex disease caused by an excessive amount of body fat. Obesity is a medical problem and represents an important risk factor for the development of serious diseases such as insulin resistance, type 2 diabetes, cardiovascular disease, and some types of cancer. Not to be overlooked are the psychological issues that, in obese subjects, turn into very serious pathologies, such as depression, phobias, anxiety, and lack of self-esteem. In addition to modifying one’s lifestyle, the reduction of body mass can be promoted by different natural compounds such as essential oils (EOs). EOs are mixtures of aromatic substances produced by many plants, particularly in medicinal and aromatic ones. They are odorous and volatile and contain a mixture of terpenes, alcohols, aldehydes, ketones, and esters. Thanks to the characteristics of the various chemical components present in them, EOs are used in the food, cosmetic, and pharmaceutical fields. Indeed, it has been shown that EOs possess great antibiotic, anti-inflammatory, and antitumor powers. Emerging results also demonstrate the anti-obesity effects of EOs. We have examined the main data obtained in experimental studies and, in this review, we summarize the effect of EOs in obesity and obesity-related metabolic diseases.
Keywords	obesity ; metabolic syndrome ; essential oils ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Parthenolide and Its Soluble Analogues

Daniela Carlisi / Marianna Lauricella / Antonella D’Anneo / Anna De Blasio / Adriana Celesia / Giovanni Pratelli / Antonietta Notaro / Giuseppe Calvaruso / Michela Giuliano / Sonia Emanuele

Biomedicines, Vol 10, Iss 514, p

Multitasking Compounds with Antitumor Properties

2022 Volume 514

Abstract: Due to its chemical properties and multiple molecular effects on different tumor cell types, the sesquiterpene lactone parthenolide (PN) can be considered an effective drug with significant potential in cancer therapy. PN has been shown to induce either ... ...

Abstract	Due to its chemical properties and multiple molecular effects on different tumor cell types, the sesquiterpene lactone parthenolide (PN) can be considered an effective drug with significant potential in cancer therapy. PN has been shown to induce either classic apoptosis or alternative caspase-independent forms of cell death in many tumor models. The therapeutical potential of PN has been increased by chemical design and synthesis of more soluble analogues including dimethylaminoparthenolide (DMAPT). This review focuses on the molecular mechanisms of both PN and analogues action in tumor models, highlighting their effects on gene expression, signal transduction and execution of different types of cell death. Recent findings indicate that these compounds not only inhibit prosurvival transcriptional factors such as NF-κB and STATs but can also determine the activation of specific death pathways, increasing intracellular reactive oxygen species (ROS) production and modifications of Bcl-2 family members. An intriguing property of these compounds is its specific targeting of cancer stem cells. The unusual actions of PN and its analogues make these agents good candidates for molecular targeted cancer therapy.
Keywords	parthenolide ; DMAPT ; apoptosis ; cell death ; cancer therapy ; NF-κB ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: p62

Sonia Emanuele / Marianna Lauricella / Antonella D’Anneo / Daniela Carlisi / Anna De Blasio / Diana Di Liberto / Michela Giuliano

International Journal of Molecular Sciences, Vol 21, Iss 5029, p

Friend or Foe? Evidences for OncoJanus and NeuroJanus Roles

2020 Volume 5029

Abstract: p62 is a versatile protein involved in the delicate balance between cell death and survival, which is fundamental for cell fate decision in the context of both cancer and neurodegenerative diseases. As an autophagy adaptor, p62 recognizes polyubiquitin ... ...

Abstract	p62 is a versatile protein involved in the delicate balance between cell death and survival, which is fundamental for cell fate decision in the context of both cancer and neurodegenerative diseases. As an autophagy adaptor, p62 recognizes polyubiquitin chains and interacts with LC3, thereby targeting the selected cargo to the autophagosome with consequent autophagic degradation. Beside this function, p62 behaves as an interactive hub in multiple signalling including those mediated by Nrf2, NF-κB, caspase-8, and mTORC1. The protein is thus crucial for the control of oxidative stress, inflammation and cell survival, apoptosis, and metabolic reprogramming, respectively. As a multifunctional protein, p62 falls into the category of those factors that can exert opposite roles in the cells. Chronic p62 accumulation was found in many types of tumors as well as in stress granules present in different forms of neurodegenerative diseases. However, the protein seems to have a Janus behaviour since it may also serve protective functions against tumorigenesis or neurodegeneration. This review describes the diversified roles of p62 through its multiple domains and interactors and specifically focuses on its oncoJanus and neuroJanus roles.
Keywords	p62 ; autophagy ; apoptosis ; cancer ; neurodegenerative diseases ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Gluten Free Diet for the Management of Non Celiac Diseases

Diana Di Liberto / Daniela Carlisi / Antonella D’Anneo / Sonia Emanuele / Michela Giuliano / Anna De Blasio / Giuseppe Calvaruso / Marianna Lauricella

Healthcare, Vol 8, Iss 400, p

The Two Sides of the Coin

2020 Volume 400

Abstract: A lifelong adherence to a gluten-free (GF) diet is currently the only treatment for Celiac disease (CD), an autoimmune disorder that arises after gluten ingestion in individuals who are genetically predisposed. The gluten intake exerts toxic effects ... ...

Abstract	A lifelong adherence to a gluten-free (GF) diet is currently the only treatment for Celiac disease (CD), an autoimmune disorder that arises after gluten ingestion in individuals who are genetically predisposed. The gluten intake exerts toxic effects through several pathways involving gut barrier integrity, intestinal microbiota composition and immune system stimulation. However, despite the great benefit of GF diet for CD patients, its use has been debated. Indeed, individuals who adopt this diet regime may be at risk of nutrient deficiencies. Emerging evidence supports a beneficial effect of a GF diet also for other pathological conditions, including gluten-related disorders (GRD) often associated to CD, such as Non celiac gluten sensitivity (NCGS) and Dermatitis Herpetiforme (DH) as well as Irritable bowel syndrome (IBS) and Diabetes. This suggests a pathogenic role of gluten in these conditions. Despite the growing popularity of GF diet among consumers, to date, there are limited evidences supporting its use for the management of non-celiac diseases. Therefore, in this review, we discuss whether the GF diet could really improve the general quality of life of patients with GRD and non-GRD conditions, keeping in mind its sensorial limitations and nutritional inadequacies. In addition, we discuss the current motivations, leading to the use of a GF diet, despite the inferior quality of GF products respect to those containing gluten.
Keywords	gluten ; non celiac disease ; gluten-free diet ; Medicine ; R
Subject code	610
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: WIN55,212-2-Induced Expression of Mir-29b1 Favours the Suppression of Osteosarcoma Cell Migration in a SPARC-Independent Manner

Antonietta Notaro / Sonia Emanuele / Fabiana Geraci / Antonella D’Anneo / Marianna Lauricella / Giuseppe Calvaruso / Michela Giuliano

International Journal of Molecular Sciences, Vol 20, Iss 20, p

2019 Volume 5235

Abstract: WIN55,212-2 (WIN) is a synthetic agonist of cannabinoid receptors that displays promising antitumour properties. The aim of this study is to demonstrate that WIN is able to block the migratory ability of osteosarcoma cells and characterize the mechanisms ...

Abstract	WIN55,212-2 (WIN) is a synthetic agonist of cannabinoid receptors that displays promising antitumour properties. The aim of this study is to demonstrate that WIN is able to block the migratory ability of osteosarcoma cells and characterize the mechanisms involved. Using wound healing assay and zymography, we showed that WIN affects cell migration and reduces the activity of the metalloproteases MMP2 and MMP9. This effect seemed to be independent of secreted protein acidic and rich in cysteine (SPARC), a matricellular protein involved in tissue remodeling and extracellular matrix deposition. SPARC release was indeed prevented by WIN, and SPARC silencing by RNA interference did not influence the effect of the cannabinoid on cell migration. WIN also increased the release of extracellular vesicles and dramatically upregulated miR-29b1, a key miRNA that modulates cell proliferation and migration. Interestingly, reduced cell migration was observed in stably miR-29b1-transfected cells, similarly to WIN-treated cells. Finally, we show the absence of SPARC in the extracellular vesicles released by osteosarcoma cells and no changes in SPARC level in miR-29b1 overexpressing cells. Overall, these findings suggest that WIN markedly affects cell migration, dependently on miR-29b1 and independently of SPARC, and can thus be considered as a potential innovative therapeutic agent in the treatment of osteosarcoma.
Keywords	osteosarcoma ; cannabinoids ; cell migration ; mir-29b1 ; sparc ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	500
Language	English
Publishing date	2019-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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