The pan-deacetylase inhibitor panobinostat affects angiogenesis in hepatocellular carcinoma models via modulation of CTGF expression

Gahr, Susanne; Mayr, Christian; Kiesslich, Tobias; Illig, Romana; Neureiter, Daniel; Alinger, Beate; Ganslmayer, Marion; Wissniowski, TT; Fazio, Pietro Di; Montalbano, Roberta; Ficker, Joachim H.; Ocker, Matthias; Quint, Karl

doi:10.3892/ijo.2015.3087

Cited by 21 publications

(10 citation statements)

References 66 publications

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“…Panobinostat is a pan-HDAC inhibitor that has been found to inhibit tumor cell proliferation, induce alternative pathways of apoptosis [91] and promote a more differentiated and less invasive phenotype in HCC cells [92]. In addition, alternative mechanisms of panobinostat activity have recently been discovered, including its ability to mediate anti-angiogenic effects via connective tissue growth factor (CTGF) pathway [93]. Moreover, panobinostat can affect cancer metabolism and tumor growth by restoring the expression of a key gluconeogenesis enzyme, fructose-1,6-bisphosphatase (FBP1), which is silenced by histone deacetylation in many cancers [79].…”

Section: Epigenetic Therapies In Hccmentioning

confidence: 99%

Epigenetics of hepatocellular carcinoma

Toh

Lim

Chow

2019

Clinical & Translational Med

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In recent years, large scale genomics and genome-wide studies using comprehensive genomic tools have reshaped our understanding of cancer evolution and heterogeneity. Hepatocellular carcinoma, being one of the most deadly cancers in the world has been well established as a disease of the genome that harbours a multitude of genetic and epigenetic aberrations during the process of liver carcinogenesis. As such, in depth understanding of the cancer epigenetics in cancer specimens and biopsy can be useful in clinical settings for molecular subclassification, prognosis, and prediction of therapeutic responses. In this review, we present a concise discussion on recent progress in the field of liver cancer epigenetics and some of the current works that contribute to the progress of liver cancer therapeutics.

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Section: Epigenetic Therapies In Hccmentioning

confidence: 99%

Epigenetics of hepatocellular carcinoma

Toh

Lim

Chow

2019

Clinical & Translational Med

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“…Panobinostat suppressed the expression of oncogenic miRNAs and promoted the maturation of the tumor suppressor miRNA in hepatocellular carcinoma cells [ 65 , 66 ]. Panobinostat can inhibit HCC proliferation and metastases by repressing the gankyrin/STAT3/Akt pathway [ 67 ] and can block the angiogenic properties of HCC by altering the CTGF signaling pathway [ 68 ]. Combination treatment involving sorafenib tosylate and panobinostat decreased vessel density, decreased tumor volume, and increased survival in HCC xenografts [ 69 ].…”

Section: Hdac Inhibitors As Clinical Trail Of Hccmentioning

confidence: 99%

Modification of Epigenetic Histone Acetylation in Hepatocellular Carcinoma

Liu

Wang

Hsu

2018

Cancers

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Cells respond to various environmental factors such as nutrients, food intake, and drugs or toxins by undergoing dynamic epigenetic changes. An imbalance in dynamic epigenetic changes is one of the major causes of disease, oncogenic activities, and immunosuppressive effects. The aryl hydrocarbon receptor (AHR) is a unique cellular chemical sensor present in most organs, and its dysregulation has been demonstrated in multiple stages of tumor progression in humans and experimental models; however, the effects of the pathogenic mechanisms of AHR on epigenetic regulation remain unclear. Apart from proto-oncogene activation, epigenetic repressions of tumor suppressor genes are involved in tumor initiation, procession, and metastasis. Reverse epigenetic repression of the tumor suppressor genes by epigenetic enzyme activity inhibition and epigenetic enzyme level manipulation is a potential path for tumor therapy. Current evidence and our recent work on deacetylation of histones on tumor-suppressive genes suggest that histone deacetylase (HDAC) is involved in tumor formation and progression, and treating hepatocellular carcinoma with HDAC inhibitors can, at least partially, repress tumor proliferation and transformation by recusing the expression of tumor-suppressive genes such as TP53 and RB1.

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“…Panobinostat is a powerful pan-HDAC inhibitor that received U.S. Food and Drug Administration (FDA) and European Medical Agency (EMA) approval for multiple myeloma treatment in 2015 [ 9 ]. Panobinostat regulates hallmarks of cancer cell biology, such as the cell cycle progression, apoptosis and angiogenesis [ 25 , 26 ]. Our results not only show the regulation of target proteins relevant to MB leptomeningeal seeding but also demonstrate the feasibility of the clinically relevant usage of panobinostat through in vivo experiments.…”

Section: Discussionmentioning

confidence: 99%

Panobinostat, a histone deacetylase inhibitor, suppresses leptomeningeal seeding in a medulloblastoma animal model

et al. 2017

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Leptomeningeal seeding is a strong negative prognostic factor for medulloblastoma (MB). The mechanism of leptomeningeal seeding is unclear but may involve epigenetic regulation. In this study, we evaluated the feasibility of a histone deacetylase (HDAC) inhibitor, panobinostat, in the suppression of MB leptomeningeal seeding.Panobinostat decreased the cell viability and proliferation, inducing cell cycle arrest and apoptosis in MB cell lines. The migration and adhesion capabilities were significantly decreased. Panobinostat effectively down-regulated protein expression of CCND1 and ID3 which has been associated with leptomeningeal seeding of MB. After panobinostat treatment, neurophil-like cellular processes developed and expression of synaptophysin and NeuroD1 was increased, indicating neuronal differentiation. In MB leptomeningeal seeding in vivo model, the panobinostat-treated group showed significantly decreased spinal leptomeningeal seeding and a survival benefit.The findings demonstrate that panobinostat suppresses MB leptomeningeal seeding through the down-regulation of ID3 and the induction of neuronal differentiation. An HDAC inhibitor might be a potent treatment option for the treatment of MB patients with leptomeningeal seeding.

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The pan-deacetylase inhibitor panobinostat affects angiogenesis in hepatocellular carcinoma models via modulation of CTGF expression

Cited by 21 publications

References 66 publications

Epigenetics of hepatocellular carcinoma

Epigenetics of hepatocellular carcinoma

Modification of Epigenetic Histone Acetylation in Hepatocellular Carcinoma

Panobinostat, a histone deacetylase inhibitor, suppresses leptomeningeal seeding in a medulloblastoma animal model

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