Arginine methyltransferase inhibitor‑1 inhibits sarcoma viability in�vitro and in�vivo

Zhang, Baolai; Chen, Xue; Ge, Suyin; Peng, Caili; Zhang, Su; Chen, Xu; Liu, Tao; Zhang, Wenkai

doi:10.3892/ol.2018.8929

Cited by 8 publications

(8 citation statements)

References 42 publications

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“…Blocking PRMT activity in many tumours has proven to be an effective way to induce apoptosis in transformed cells of osteosarcoma, colorectal cancer, lung cancer and melanoma [ 29 , 49 , 53 , 54 ]. We have shown that AMI-1 and SAH significantly affect the level of histone arginine methylation at H3R2me2a, H3R8me2s, H3R17me2a, H4R3me2a ( Figure 5 ) In our study, we observed that the use of AMI-1 and SAH in RMS cells also resulted in a statistically significant increase in apoptosis ( Figure 3 B).…”

Section: Discussionmentioning

confidence: 99%

Protein Arginine Methyltransferase (PRMT) Inhibitors—AMI-1 and SAH Are Effective in Attenuating Rhabdomyosarcoma Growth and Proliferation in Cell Cultures

Janisiak

Kopytko

Tkacz

et al. 2021

IJMS

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Rhabdomyosarcoma (RMS) is a malignant soft tissue cancer that develops mostly in children and young adults. With regard to histopathology, four rhabdomyosarcoma types are distinguishable: embryonal, alveolar, pleomorphic and spindle/sclerosing. Currently, increased amounts of evidence indicate that not only gene mutations, but also epigenetic modifications may be involved in the development of RMS. Epigenomic changes regulate the chromatin architecture and affect the interaction between DNA strands, histones and chromatin binding proteins, thus, are able to control gene expression. The main aim of the study was to assess the role of protein arginine methyltransferases (PRMT) in the cellular biology of rhabdomyosarcoma. In the study we used two pan-inhibitors of PRMT, called AMI-1 and SAH, and evaluated their effects on proliferation and apoptosis of RMS cells. We observed that AMI-1 and SAH reduce the invasive phenotype of rhabdomyosarcoma cells by decreasing their proliferation rate, cell viability and ability to form cell colonies. In addition, microarray analysis revealed that these inhibitors attenuate the activity of the PI3K-Akt signaling pathway and affect expression of genes related to it.

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Section: Discussionmentioning

confidence: 99%

Protein Arginine Methyltransferase (PRMT) Inhibitors—AMI-1 and SAH Are Effective in Attenuating Rhabdomyosarcoma Growth and Proliferation in Cell Cultures

Janisiak

Kopytko

Tkacz

et al. 2021

IJMS

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“…Initially, AMI-1 was used to inhibit type I PRMTs (PRMT1- PRMT4, PRMT6, and PRMT8) in vitro [ 17 ]. However, further studies showed that the effect of AMI-1 on suppressing the proliferation of solid tumors (e.g., hepatocellular carcinoma, colorectal cancer, and gastric cancer) is mediated by inhibiting type II PRMT5 [ 26 , 27 ]. Most studies that exploited the anti-tumor potential of AMI-1 by targeting PRMT5 used a high dose of AMI-1 (in the mM range) [ 26 , 27 , 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…One of the limitations of our study is that the effect of targeting PRMT1 by AMI-1 was not investigated. However, previous studies showed that the anti-tumor effect of AMI-1 is rather mediated through PRMT5 [ 26 , 27 ]. Another limitation is to precisely define the subcellular localization of PRMT5, which requires nuclear extraction.…”

Section: Discussionmentioning

confidence: 99%

PRMT5 Selective Inhibitor Enhances Therapeutic Efficacy of Cisplatin in Lung Cancer Cells

Bajbouj

Ramakrishnan

Saber-Ayad

et al. 2021

IJMS

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As a therapeutic approach, epigenetic modifiers have the potential to enhance the efficacy of chemotherapeutic agents. Protein arginine methyltransferase 5 (PRMT5), highly expressed in lung adenocarcinoma, was identified to be involved in tumorigenesis. In the current study, we examined the potential antineoplastic activity of PRMT5 inhibitor, arginine methyltransferase inhibitor 1 (AMI-1), and cisplatin on lung adenocarcinoma. Bioinformatic analyses identified apoptosis, DNA damage, and cell cycle progression as the main PRMT5-associated functional pathways, and survival analysis linked the increased PRMT5 gene expression to worse overall survival in lung adenocarcinoma. Combined AMI-1 and cisplatin treatment significantly reduced cell viability and induced apoptosis. Cell cycle arrest in A549 and DMS 53 cells was evident after AMI-1, and was reinforced after combination treatment. Western blot analysis showed a reduction in demethylation histone 4, a PRMT5- downstream target, after treatment with AMI-1 alone or in combination with cisplatin. While the combination approach tackled lung cancer cell survival, it exhibited cytoprotective abilities on HBEpC (normal epithelial cells). The survival of normal bronchial epithelial cells was not affected by using AMI-1. This study highlights evidence of novel selective antitumor activity of AMI-1 in combination with cisplatin in lung adenocarcinoma cells.

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“…Indeed, we find that sole deletion of PRMT5 in T cells is sufficient to halt multiple aspects of severe lung inflammation. It is important to note that, at least in T cells, PRMT5 has been found to regulate PRMT1 in a positive feedback loop (27)(28)(29)(30). Therefore, part of PRMT5's effects could be indirectly mediated by PRMT1 induction.…”

Section: Discussionmentioning

confidence: 99%

PRMT5 in T cells drives Th17 responses, mixed granulocytic inflammation and severe allergic airway inflammation

Lewis

Amici

Kim

et al. 2021

Preprint

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Severe asthma is characterized by steroid insensitivity and poor symptom control, and is responsible for the majority of asthma-related hospital costs. Therapeutic options remain limited, in part due to a lack of mechanisms driving severe asthma phenotypes. Increased arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), is increased in asthmatic lungs. Here, we show that PRMT5 drives allergic airway inflammation in a mouse model reproducing multiple aspects of human severe asthma. We find that PRMT5 is required in CD4+ T cells for chronic steroid-insensitive severe lung inflammation, with selective T cell deletion of PRMT5 robustly suppressing eosinophilic and granulocytic lung inflammation, pathology, airway remodeling and hyperresponsiveness. Mechanistically, we observed high pulmonary sterol metabolic activity, ROR-γt and Th17 responses, with PRMT5-dependent increases in ROR-γt agonist desmosterol. Our work demonstrates that T cell PRMT5 drives severe allergic lung inflammation and has potential implications for the pathogenesis and therapeutic targeting of severe asthma.

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Arginine methyltransferase inhibitor‑1 inhibits sarcoma viability in�vitro and in�vivo

Cited by 8 publications

References 42 publications

Protein Arginine Methyltransferase (PRMT) Inhibitors—AMI-1 and SAH Are Effective in Attenuating Rhabdomyosarcoma Growth and Proliferation in Cell Cultures

Protein Arginine Methyltransferase (PRMT) Inhibitors—AMI-1 and SAH Are Effective in Attenuating Rhabdomyosarcoma Growth and Proliferation in Cell Cultures

PRMT5 Selective Inhibitor Enhances Therapeutic Efficacy of Cisplatin in Lung Cancer Cells

PRMT5 in T cells drives Th17 responses, mixed granulocytic inflammation and severe allergic airway inflammation

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