Valproic acid induces neuronal cell death through a novel calpain‐dependent necroptosis pathway

Bollino, Dominique; Balan, Irina; Aurelian, Laure

doi:10.1111/jnc.13029

Cited by 41 publications

(30 citation statements)

References 75 publications

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“…The lack of apoptosis induction was verified by FACS analyses demonstrating that the PN did not increase the number of annexin V positive (apoptotic) cells, but instead induced a G2 cell cycle arrest in melanoma cells and increased the percentage of PI-positive (necrotic) cells. Necroptosis (the programmed form of necrosis, or inflammatory cell death), which is driven by TNFα, has recently been shown to be altered in neuronal cells by HDAC inhibitors such as SAHA (protects from necroptosis [34]) and VPA (induces necroptosis [35]). In malignantly transformed acute myeloid leukemia cells the HDACi MS275 enhanced necroptosis [36]).…”

Section: Discussionmentioning

confidence: 99%

6- and 8-Prenylnaringenin, Novel Natural Histone Deacetylase Inhibitors Found in Hops, Exert Antitumor Activity on Melanoma Cells

Venturelli

Niessner

Sinnberg

et al. 2018

Cell Physiol Biochem

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Background/Aims: Prenylnaringenins are natural prenylflavonoids with anticancer properties. However, the underlying mechanisms have not been elucidated yet. Here we report a novel mode of action of 6- and 8-prenylnaringenin (PN) on human melanoma cells: Inhibition of cellular histone deacetylases (HDACs). Methods: We performed in silico and in vitro analyses using 6-PN or 8-PN to study a possible interaction of 6-PN or 8-PN with HDAC as well as Western blot and FACS analyses, real-time cell proliferation and cell viability assays to assess the impact of 6-PN and 8-PN on human metastatic melanoma cells. Results: In silico, 6-PN and 8-PN fit into the binding pocket of HDAC2, 4, 7 and 8, binding to the zinc ion of their catalytic center that is essential for enzymatic activity. In vitro, 100 µmol/L of 6-PN or 8-PN inhibited all 11 conserved human HDAC of class I, II and IV. In clinical oncology HDAC inhibitors are currently investigated as new anticancer compounds. In line, treatment of SK-MEL-28 cells with 6-PN or 8-PN induced a hyperacetylation of histone complex H3 within 2 h. Further, 6-PN or 8-PN mediated a prominent, dose-dependent reduction of cellular proliferation and viability of SK-MEL-28 and BLM melanoma cells. This effect was apoptosis-independent and accompanied by down-regulation of mTOR-specific pS6 protein via pERK/pP90 in SK-MEL-28 cells. Conclusion: The identification of a broad inhibitory capacity of 6-PN and 8-PN for HDAC enzymes with antiproliferative effects on melanoma cells opens the perspective for clinical application as novel anti-melanoma drugs and the usage as innovative lead structures for chemical modification to enhance pharmacology or inhibitory activities.

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Section: Discussionmentioning

confidence: 99%

6- and 8-Prenylnaringenin, Novel Natural Histone Deacetylase Inhibitors Found in Hops, Exert Antitumor Activity on Melanoma Cells

Venturelli

Niessner

Sinnberg

et al. 2018

Cell Physiol Biochem

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“…Meanwhile, suppression of both neuronal cell apoptosis and necroptosis was observed by a new high-affinity TrkB agonistic antibody which thus reduced the infarct size and facilitated functional recovery in the rat MCAO model [10]. Experimental evidence from other disease models suggests this antinecroptotic effect may be mediated by the MAPK/ERK and PI3K/Akt pathways [59,60]. Although more investigations are needed, these newly discovered neuronal cell death types may serve as novel targets for stroke treatment in the future (extensively reviewed by Fricker et al [61]).…”

Section: Role Of Bdnf In Stroke Andmentioning

confidence: 99%

Brain-Derived Neurotrophic Factor and Its Potential Therapeutic Role in Stroke Comorbidities

et al. 2020

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With the rise in the aging global population, stroke comorbidities have become a serious health threat and a tremendous economic burden on human society. Current therapeutic strategies mainly focus on protecting neurons from cytotoxic damage at the acute phase upon stroke onset, which not only is a difficult way to ameliorate stroke symptoms but also presents a challenge for the patients to receive effective treatment in time. The brain-derived neurotrophic factor (BDNF) is the most abundant neurotrophin in the adult brain, which possesses a remarkable capability to repair brain damage. Recent promising preclinical outcomes have made BDNF a popular late-stage target in the development of novel stroke treatments. In this review, we aim to summarize the latest progress in the understanding of the cellular/molecular mechanisms underlying stroke pathogenesis, current strategies and difficulties in drug development, the mechanism of BDNF action in poststroke neurorehabilitation and neuroplasticity, and recent updates in novel therapeutic methods.

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“…Separation of cytoplasmic/nuclear fractions and immunoblotting were done as described previously (Bollino et al, 2015;Wales et al, 2008).…”

Section: Dpk Oncolytic Activity Includes Immunomodulationmentioning

confidence: 99%

ΔPK oncolytic activity includes modulation of the tumour cell milieu

Bollino

Nghiem

et al. 2016

Journal of General Virology

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Oncolytic virotherapy is a unique cancer therapeutic that encompasses tumour cell lysis through both virus replication and programmed cell death (PCD) pathways. Nonetheless, clinical efficacy is relatively modest, likely related to the immunosuppressive tumour milieu. Our studies use the herpes simplex virus type 2 (HSV-2)-based oncolytic virus D PK that has documented anti-tumour activity associated with virus replication, PCD and cancer stem cell lysis. They are designed to examine whether D PK-mediated oncolysis includes the ability to reverse the immunosuppressive tumour microenvironment by altering the balance of cytokines directly secreted by the melanoma cells and to define its mechanism. Here, we show that melanoma cells secreted the immunosuppressive cytokine IL-10, and that secretion was inhibited by D PK through virus replication and c-Jun N-terminal kinase/c-Jun activation. D PK-induced IL-10 inhibition upregulated surface expression of MHC class I chain-related protein A, the ligand for the activating NKG2D receptor expressed on NK-and cytotoxic T-cells. Concomitantly, D PK also upregulated the secretion of inflammatory cytokines TNF-a, granulocyte macrophage colony-stimulating factor and IL-1b through autophagy-mediated activation of Toll-like receptor 2 pathways and pyroptosis, and it inhibited the expression of the negative immune checkpoint regulator cytotoxic T-lymphocyte antigen 4. Pharmacologic inhibition of these processes significantly reduces the oncolytic activity of D PK.

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Valproic acid induces neuronal cell death through a novel calpain‐dependent necroptosis pathway

Cited by 41 publications

References 75 publications

6- and 8-Prenylnaringenin, Novel Natural Histone Deacetylase Inhibitors Found in Hops, Exert Antitumor Activity on Melanoma Cells

6- and 8-Prenylnaringenin, Novel Natural Histone Deacetylase Inhibitors Found in Hops, Exert Antitumor Activity on Melanoma Cells

Brain-Derived Neurotrophic Factor and Its Potential Therapeutic Role in Stroke Comorbidities

ΔPK oncolytic activity includes modulation of the tumour cell milieu

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