Differentially activated Src kinase in chemo‐naïve human primary osteosarcoma cells and effects of a Src kinase inhibitor

Laschi, Marcella; Bernardini, Giulia; Geminiani, Michela; Manetti, Fabrizio; Mori, Mattia; Spreafico, Adriano; Campanacci, Domenico Andrea; Capanna, Rodolfo; Schenone, Silvia; Botta, Maurizio; Santucci, Annalisa

doi:10.1002/biof.1382

Cited by 8 publications

(8 citation statements)

References 27 publications

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“…Moreover, consistent with the above described role of SFKs in cell invasiveness, dasatinib also decreased MM cell migration and invasion ability [32,53]. Our pyrazolo-[3,4-d]-pyrimidine derivatives, which proved to be promising anticancer agents in several tumor types [44,49,[111][112][113][114][115][116][117][118][119][120], had a significant antiproliferative effect selectively in MM cells with SFK hyperactivation [49]. Moreover, these molecules induced apoptosis only on cancer cells, without affecting normal mesothelial cells.…”

Section: Antitumor Activity Of Sfk Inhibitors In MM Cell Lines and Unsupporting

confidence: 84%

Targeting SRC Family Kinases in Mesothelioma: Time to Upgrade

Indovina

Forte

Pentimalli

et al. 2020

Cancers

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Malignant mesothelioma (MM) is a deadly tumor mainly caused by exposure to asbestos. Unfortunately, no current treatment is able to change significantly the natural history of the disease, which has a poor prognosis in the majority of patients. The non-receptor tyrosine kinase SRC and other SRC family kinase (SFK) members are frequently hyperactivated in many cancer types, including MM. Several works have indeed suggested that SFKs underlie MM cell proliferation, survival, motility, and invasion, overall affecting multiple oncogenic pathways. Consistently, SFK inhibitors effectively counteracted MM cancerous features at the preclinical level. Dasatinib, a multi-kinase inhibitor targeting SFKs, was also assessed in clinical trials either as second-line treatment for patients with unresectable MM or, more recently, as a neoadjuvant agent in patients with resectable MM. Here, we provide an overview of the molecular mechanisms implicating SFKs in MM progression and discuss possible strategies for a more successful clinical application of SFK inhibitors. Our aim is to stimulate discussion and further consideration of these agents in better designed preclinical and clinical studies to make the most of another class of powerful antitumoral drugs, which too often are lost in translation when applied to MM.

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Section: Antitumor Activity Of Sfk Inhibitors In MM Cell Lines and Unsupporting

confidence: 84%

Targeting SRC Family Kinases in Mesothelioma: Time to Upgrade

Indovina

Forte

Pentimalli

et al. 2020

Cancers

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“…The principal candidate drugs were anti-cancer drugs associated with proto-oncogene tyrosine-protein kinase Src (SRC). Studies have suggested that SRC is involved in the development and progression of certain cancer types ( 48 , 49 ). The identified candidate miRNA was miR-29B, which is able to suppress the progression of tumors and prevent liver fibrosis, indicating that it may be an effective therapeutic target for NAFLD-associated fibrosis and HCC ( 50 – 52 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of key genes in non‑alcoholic fatty liver disease progression based on bioinformatics analysis

Liu

et al. 2018

Mol Med Report

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Due to economic development and lifestyle changes, the incidence of non-alcoholic fatty liver disease (NAFLD) has gradually increased in recent years. However, the pathogenesis of NAFLD is not yet fully understood. To identify candidate genes that contribute to the development and progression of NAFLD, two microarray datasets were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified and functional enrichment analyses were performed. A protein-protein interaction network was constructed and modules were extracted using the Search Tool for the Retrieval of Interacting Genes and Cytoscape. The enriched functions and pathways of the DEGs included ‘cellular macromolecule biosynthetic process’, ‘cellular response to chemical stimulus’, ‘extracellular matrix organization’, ‘metabolic pathways’, ‘insulin resistance’ and ‘forkhead box protein O1 signaling pathway’. The DEGs, including type-1 angiotensin II receptor, formin-binding protein 1-like, RNA-binding protein with serine-rich domain 1, Ras-related C3 botulinum toxin substrate 1 and polyubiquitin-C, were identified using multiple bioinformatics methods and validated in vitro with reverse transcription-quantitative polymerase chain reaction analysis. In conclusion, five hub genes were identified in the present study, and they may aid in understanding of the molecular mechanisms underlying the development and progression of NAFLD.

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“…Human OS SaOS-2 (ATCC-HTB-85) and MNNG (ATCC-CRL-1547) cells were obtained from American Type Culture Collection (ATCC, Manassas, VA, USA) and cultured as described [71,72,73] in DMEM containing 10% v/v FBS, 100 mg/mL penicillin and 100 mg/mL streptomycin. Cultures were mainteined at 37 °C in a humidified atmosphere of 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

Pro-Apoptotic Activity of French Polynesian Padina pavonica Extract on Human Osteosarcoma Cells

Bernardini

Minetti

Polizzotto³

et al. 2018

Marine Drugs

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Recently, seaweeds and their extracts have attracted great interest in the pharmaceutical industry as a source of bioactive compounds. Studies have demonstrated the cytotoxic activity of macroalgae towards different types of cancer cell models, and their consumption has been suggested as a chemo-preventive agent against several cancers such as breast, cervix and colon cancers. Reports relevant to the chemical properties of brown algae Padina sp. are limited and those accompanied to a comprehensive evaluation of the biological activity on osteosarcoma (OS) are non existent. In this report, we explored the chemical composition of French Polynesian Padina pavonica extract (EPP) by spectrophotometric assays (total phenolic, flavonoid and tannin content, and antioxidant activity) and by gas chromatography-mass spectrometry (GC-MS) analysis, and provided EPP lipid and sterols profiles. Several compounds with relevant biological activity were also identified that suggest interesting pharmacological and health-protecting effects for EPP. Moreover, we demonstrated that EPP presents good anti-proliferative and pro-apoptotic activities against two OS cell lines, SaOS-2 and MNNG, with different cancer-related phenotypes. Finally, our data suggest that EPP might target different properties associated with cancer development and aggressiveness.

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Differentially activated Src kinase in chemo‐naïve human primary osteosarcoma cells and effects of a Src kinase inhibitor

Cited by 8 publications

References 27 publications

Targeting SRC Family Kinases in Mesothelioma: Time to Upgrade

Targeting SRC Family Kinases in Mesothelioma: Time to Upgrade

Identification of key genes in non‑alcoholic fatty liver disease progression based on bioinformatics analysis

Pro-Apoptotic Activity of French Polynesian Padina pavonica Extract on Human Osteosarcoma Cells

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