A Pyrazolo[3,4-d]pyrimidine Compound Reduces Cell Viability and Induces Apoptosis in Different Hematological Malignancies

Laurenzana, Ilaria; Caivano, Antonella; Rocca, Francesco La; Trino, Stefania; Luca, Luciana De; D’Alessio, Francesca; Schenone, Silvia; Falco, Geppino; Botta, Maurizio; Vecchio, Luigi Del; Musto, Pellegrino

doi:10.3389/fphar.2016.00416

Cited by 9 publications

(7 citation statements)

References 40 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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“…Cell viability was assessed using the MTS assay [ 71 , 72 ]. In brief, cells were seeded into 96-well plates (3 × 10 4 cell/100 µL medium), treated with AG samples at different concentrations (10, 50, 100, and 150 µg/mL), and incubated for 24, 48, and 72 h. The optical density was measured at 492 nm.…”

Section: Methodsmentioning

confidence: 99%

Future in the Past: Azorella glabra Wedd. as a Source of New Natural Compounds with Antiproliferative and Cytotoxic Activity on Multiple Myeloma Cells

Lamorte

Faraone

Laurenzana

et al. 2018

IJMS

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Multiple myeloma (MM) is the second most common hematologic malignancy and, although the development of novel agents has improved survival of patients, to date, it remains incurable. Thus, newer and more effective therapeutic strategies against this malignancy are necessary. Plant extracts play an important role in anti-tumor drug discovery. For this reason, in the investigation of novel natural anti-MM agents, we evaluated the phytochemical profiles, in vitro antioxidant activity, and effects on MM cells of Azorella glabra (AG) Wedd. Total polyphenols (TPC), flavonoids (TFC), and terpenoids (TTeC) contents were different among samples and the richest fractions in polyphenols demonstrated a higher antioxidant activity in in vitro assays. Some fractions showed a dose and time dependent anti-proliferative activity on MM cells. The chloroform fraction (CHCl3) showed major effects in terms of reduction of cell viability, induction of apoptosis, and cell cycle arrest on MM cells. The apoptosis induction was also confirmed by the activation of caspase-3. Importantly, the CHCl3 fraction exhibited a negligible effect on the viability of healthy cells. These results encourage further investigations on AG extracts to identify specific bioactive compounds and to define their potential applications in MM.

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“…Cell cycle analysis was performed as described by Laurenzana et al [ 34 ]. Briefly, HepG2 cells (2 × 10 5 cells/well) were seeded into 12-well plates and treated with 250 µM probenecid or 0.25% DMSO (vehicle) for 24 and 48 h. Cells were then harvested, washed once with ice-cold PBS, fixed in cold 70% ethanol, and stained with propidium iodide staining solution (50 μg/mL PI and 10 μg/mL RNase) for 30 min in the dark.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of ABCC6 Transporter Modifies Cytoskeleton and Reduces Motility of HepG2 Cells via Purinergic Pathway

Ostuni

Carmosino

Miglionico

et al. 2020

Cells

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ABCC6, belonging to sub-family C of ATP-binding cassette transporter, is an ATP-dependent transporter mainly present in the basolateral plasma membrane of hepatic and kidney cells. Although the substrates transported are still uncertain, ABCC6 has been shown to promote ATP release. The extracellular ATP and its derivatives di- and mono-nucleotides and adenosine by acting on specific receptors activate the so-called purinergic pathway, which in turn controls relevant cellular functions such as cell immunity, inflammation, and cancer. Here, we analyzed the effect of Abcc6 knockdown and probenecid-induced ABCC6 inhibition on cell cycle, cytoskeleton, and motility of HepG2 cells. Gene and protein expression were evaluated by quantitative Reverse Transcription PCR (RT-qPCR) and western blot, respectively. Cellular cycle analysis was evaluated by flow cytometry. Actin cytoskeleton dynamics was evaluated by laser confocal microscopy using fluorophore-conjugated phalloidin. Cell motility was analyzed by in vitro wound-healing migration assay. Cell migration is reduced both in Abcc6 knockdown HepG2 cells and in probenecid treated HepG2 cells by interfering with the extracellular reserve of ATP. Therefore, ABCC6 could contribute to cytoskeleton rearrangements and cell motility through purinergic signaling. Altogether, our findings shed light on a new role of the ABCC6 transporter in HepG2 cells and suggest that its inhibitor/s could be considered potential anti-metastatic drugs.

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A Pyrazolo[3,4-d]pyrimidine Compound Reduces Cell Viability and Induces Apoptosis in Different Hematological Malignancies

Cited by 9 publications

References 40 publications

Targeting SRC Family Kinases in Mesothelioma: Time to Upgrade

Targeting SRC Family Kinases in Mesothelioma: Time to Upgrade

Future in the Past: Azorella glabra Wedd. as a Source of New Natural Compounds with Antiproliferative and Cytotoxic Activity on Multiple Myeloma Cells

Inhibition of ABCC6 Transporter Modifies Cytoskeleton and Reduces Motility of HepG2 Cells via Purinergic Pathway

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