c-Myc Inhibition Using 10058-F4 Increased the Sensitivity of Acute Promyelocytic Leukemia Cells to Arsenic Trioxide Via Blunting PI3K/NF-κB Axis

Sayyadi, Mohammad; Safaroghli‐Azar, Ava; Pourbagheri‐Sigaroodi, Atieh; Abolghasemi, Hassan; Anoushirvani, Ali Arash; Bashash, Davood

doi:10.1016/j.arcmed.2020.06.002

Cited by 15 publications

(7 citation statements)

References 20 publications

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“…e aberrant expression of antiapoptotic Bcl-2 family proteins is firmly linked with chemoresistance and poor prognosis [15]. 10058-F4 is a c-Myc inhibitor that explicitly inhibits c-Myc-Max interactions and prevents the transcriptional activation of c-Myc target gene expression [16][17][18][19]. 10058-F4 can promote caspase-3-dependent apoptosis and regulate autophagy.…”

Section: Methodsmentioning

confidence: 99%

Targeting AraC-Resistant Acute Myeloid Leukemia by Dual Inhibition of CDK9 and Bcl-2: A Systematic Review and Meta-Analysis

Han

et al. 2022

Journal of Healthcare Engineering

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Purpose. This study aims to determine the influence of targeting araC-resistant acute myeloid leukemia by dual inhibition cyclin-dependent protein kinase (CDK9) and B-cell lymphoma-2 （Bcl-2). Method. The c-Myc inhibitor 10058-F4 and the CDK9 inhibitor AZD4573 were used to determine the cell cycle arrest and apoptosis. Results. 10058-F4 reduces c-Myc protein levels and suppresses HepG2 cell proliferation, possibly by upregulating cyclin-dependent kinase (CDK) inhibitors, p21WAF1, and reducing intracellular alpha-fetal protein (AFP) levels. Conclusion. The combination of AZD4573 and 10058-F4 has a synergistic anti-araC-resistant AML activity, providing a solid database for the aforementioned scientific hypothesis.

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Section: Methodsmentioning

confidence: 99%

Targeting AraC-Resistant Acute Myeloid Leukemia by Dual Inhibition of CDK9 and Bcl-2: A Systematic Review and Meta-Analysis

Han

et al. 2022

Journal of Healthcare Engineering

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“… 150 , 151 The same compound could also improve the sensitivity of acute promyelocytic leukemia (APL) to arsenic trioxide. 152 Treatment with 10,058-F4 also reduced pancreatic cancer cells viability by accelerating their apoptosis. It partly inhibited glycolysis and led to pancreatic cancer cell cycle arrest at G1/S transition.…”

Section: The Effect Of C-myc On Cancer Cells Metabolismmentioning

confidence: 96%

Target c-Myc to treat pancreatic cancer

Ala

2022

Cancer Biology & Therapy

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C-Myc overexpression is a common finding in pancreatic cancer and predicts the aggressive behavior of cancer cells. It binds to the promoter of different genes, thereby regulating their transcription. C-Myc is downstream of KRAS and interacts with several oncogenic and proliferative pathways in pancreatic cancer. C-Myc enhances aerobic glycolysis in cancer cells and regulates glutamate biosynthesis from glutamine. It provides enough energy for cancer cells’ metabolism and sufficient substrate for the synthesis of organic molecules. C-Myc overexpression is associated with chemoresistance, intra-tumor angiogenesis, epithelial-mesenchymal transition (EMT), and metastasis in pancreatic cancer. Despite its title, c-Myc is not “undruggable” and recent studies unveiled that it can be targeted, directly or indirectly. Small molecules that accelerate c-Myc ubiquitination and degradation have been effective in preclinical studies. Small molecules that hinder c-Myc-MAX heterodimerization or c-Myc/MAX/DNA complex formation can functionally inhibit c-Myc. In addition, c-Myc can be targeted through transcriptional, post-transcriptional, and translational modifications.

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“…These data added new knowledge to the regulatory function of WTAP and Myc in facilitating NF‐κB signaling. 39 , 40 More interestingly, OS could downregulate WTAP‐mediated TGM2 mRNA m 6 A modification and Myc‐mediated WTAP transcription to restrain the activation of the TGM2/Myc/WTAP‐positive feedback loop. Importantly, OS regulated key effectors identified in the dysregulated network to delay RA progression and improved the anti‐RA effect of MTX in the CIA mouse model without obvious side effects, suggesting OS as an effective anti‐RA effect drug candidate.…”

Section: Discussionmentioning

confidence: 99%

Osthole regulates N6‐methyladenosine‐modified TGM2 to inhibit the progression of rheumatoid arthritis and associated interstitial lung disease

Lin

Chen

Tao

et al. 2023

MedComm

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Rheumatoid arthritis (RA) is an inflammatory autoimmune disease, and RA interstitial lung disease (ILD) is a severe complication of RA. This investigation aims to determine the effect and underlying mechanism of osthole (OS), which could be extracted from Cnidium , Angelica , and Citrus plants and evaluate the role of transglutaminase 2 (TGM2) in RA and RA‐ILD. In this work, OS downregulated TGM2 to exert its additive effect with methotrexate and suppress the proliferation, migration, and invasion of RA‐fibroblast‐like synoviocytes (FLS) by attenuating NF‐κB signaling, resulting in the suppression of RA progression. Interestingly, WTAP‐mediated N6‐methyladenosine modification of TGM2 and Myc‐mediated WTAP transcription cooperatively contributed to the formation of a TGM2/Myc/WTAP‐positive feedback loop through upregulating NF‐κB signaling. Moreover, OS could downregulate the activation of the TGM2/Myc/WTAP‐positive feedback circuit. Furthermore, OS restrained the proliferation and polarization of M2 macrophages to inhibit the aggregation of lung interstitial CD11b + macrophages, and the effectiveness and non‐toxicity of OS in suppressing RA and RA‐ILD progression were verified in vivo. Finally, bioinformatics analyses validated the importance and the clinical significance of the OS‐regulated molecular network. Taken together, our work emphasized OS as an effective drug candidate and TGM2 as a promising target for RA and RA‐ILD treatment.

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c-Myc Inhibition Using 10058-F4 Increased the Sensitivity of Acute Promyelocytic Leukemia Cells to Arsenic Trioxide Via Blunting PI3K/NF-κB Axis

Cited by 15 publications

References 20 publications

Targeting AraC-Resistant Acute Myeloid Leukemia by Dual Inhibition of CDK9 and Bcl-2: A Systematic Review and Meta-Analysis

Targeting AraC-Resistant Acute Myeloid Leukemia by Dual Inhibition of CDK9 and Bcl-2: A Systematic Review and Meta-Analysis

Target c-Myc to treat pancreatic cancer

Osthole regulates N6‐methyladenosine‐modified TGM2 to inhibit the progression of rheumatoid arthritis and associated interstitial lung disease

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