Azelaic Acid Exerts Antileukemic Activity in Acute Myeloid Leukemia

Pan, Yunbao; Liu, Dong; Wei, Yongchang; Su, Dan; Lu, Chenyang; Hu, Yanchao; Zhou, Fuling

doi:10.3389/fphar.2017.00359

Cited by 17 publications

(17 citation statements)

References 23 publications

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“…Mitochondrial damage results in mitochondrial ROS production, which upregulates the expression of p53, which promotes mitochondria-mediated apoptosis [ 81 ]. In fact, it has recently been confirmed that AZA induces apoptosis in acute myeloid leukaemia cells in a dose-dependent manner [ 82 ]. Thus, AZA shares mechanistic similarities with peroxide-induced mitochondrial disturbances upregulating the p53 response.…”

Section: Azelaic Acidmentioning

confidence: 99%

p53: key conductor of all anti-acne therapies

Melnik

2017

J Transl Med

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This review based on translational research predicts that the transcription factor p53 is the key effector of all anti-acne therapies. All-trans retinoic acid (ATRA) and isotretinoin (13-cis retinoic acid) enhance p53 expression. Tetracyclines and macrolides via inhibiting p450 enzymes attenuate ATRA degradation, thereby increase p53. Benzoyl peroxide and hydrogen peroxide elicit oxidative stress, which upregulates p53. Azelaic acid leads to mitochondrial damage associated with increased release of reactive oxygen species inducing p53. p53 inhibits the expression of androgen receptor and IGF-1 receptor, and induces the expression of IGF binding protein 3. p53 induces FoxO1, FoxO3, p21 and sestrin 1, sestrin 2, and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), the key inducer of isotretinoin-mediated sebocyte apoptosis explaining isotretinoin’s sebum-suppressive effect. Anti-androgens attenuate the expression of miRNA-125b, a key negative regulator of p53. It can thus be concluded that all anti-acne therapies have a common mode of action, i.e., upregulation of the guardian of the genome p53. Immortalized p53-inactivated sebocyte cultures are unfortunate models for studying acne pathogenesis and treatment.

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Section: Azelaic Acidmentioning

confidence: 99%

p53: key conductor of all anti-acne therapies

Melnik

2017

J Transl Med

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“…Acute myeloid leukaemia (AML) is a heterogeneous group of disorders characterized by the clonal proliferation of progenitor cells or primitive hematopoietic stem cells (1). Due to the development of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with AML, in particular the extensive development of haploidentical allo-HSCT in China, the therapeutic efficacy of treatments for AML have significantly improved throughout previous decades (2). However, the treatment of refractory and relapsed patients remains a significant clinical challenge that has yet to be overcome (3).…”

Section: Introductionmentioning

confidence: 99%

Mutational spectrum and associations with clinical features in patients with acute myeloid leukaemia based on next‑generation sequencing

Liu

et al. 2019

Mol Med Report

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The aim of the present study was to examine the associations between 112 acute myeloid leukaemia (AML)-associated genes and the prognosis and clinical features of AML using bioinformatics analysis in 62 patients with AML. A total of 61 gene mutations were identified, and ≥1 mutations were detected in 96.77% of the patients. A total of 11 frequent mutations were identified, including nucleophosmin 1 ( NPM1 ), Fms related tyrosine kinase 3 ( FLT3 ), DNA methyltransferase 3α (DNMT3A) and Notch 2 ( NOTCH2 ), with a mutation rate of ≥10%. The FLT3 mutation was significantly associated with the white blood cell count at the time of diagnosis, and DNMT3A was significantly associated with the French-American-British subtype and cytogenetics of patients with AML. The FLT3, NPM1 and DNMT3A mutations were significantly associated with a poor overall survival (OS) in patients with AML. In addition, the co-mutation of DNMT3A -CCAAT enhancer binding protein α ( CEBPA ) was observed to be significantly associated with a poor OS in patients with AML. Furthermore, the functional enrichment analysis revealed that the co-mutations of FLT3-NOTCH2, SETBP1-CREBBP and DNMT3A-CEBPA were significantly enriched in processes of ‘negative regulation of cell differentiation’ and ‘immune system development’, indicating that these mutations may serve crucial roles in the diagnosis and treatment of AML.

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“…Azelaic acid is a naturally occurring saturated dicarboxylic acid derived from a variety of grains such as sorghum ( Sorghum bicolor ) [66], rye ( Secale cereal ) [67]. This compound has also been reported to exert a variety of biological activities in vitro and in vivo including antimicrobial [46] and antitumor [47,48] capabilities. The U.S. Food and Drug Administration (FDA) approved 15% gel formulation of azelaic acid for the treatment of rosacea in 2002 [68] and this compound is an excellent antimicrobial agent cosmetic for the treatment of comedonal and inflammatory acnes [69,70].…”

Section: Discussionmentioning

confidence: 99%

Identifying Antibacterial Compounds in Black Walnuts (Juglans nigra) Using a Metabolomics Approach

Lei

Sumner

et al. 2018

Metabolites

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Black walnut (Juglans nigra L.) is one of the most economically valuable hardwood species and a high value tree for edible nut production in the United States. Although consumption of black walnut has been linked to multiple health-promoting effects (e.g., antioxidant, antimicrobial, anti-inflammatory), the bioactive compounds have not been systematically characterized. In addition, the associations between different black walnut cultivars and their health-promoting compounds have not been well established. In this study, the kernels of twenty-two black walnut cultivars selected for nut production by the University of Missouri Center for Agroforestry (Columbia, MO, USA) were evaluated for their antibacterial activities using agar-well diffusion assay. Among the selected cultivars, four black walnut cultivars (i.e., Mystry, Surprise, D.34, and A.36) exhibited antibacterial activity against a Gram-positive bacterium (Staphylococcus aureus), whereas other cultivars showed no effect on the inhibition of this bacterium. The antibacterial compounds showing the strongest activity were isolated with bioassay-guided purification and identified using a metabolomics approach. Six antibacterial bioactive compounds responsible for antimicrobial activity were successfully identified. Glansreginin A, azelaic acid, quercetin, and eriodictyol-7-O-glucoside are novel antibacterial compounds identified in the kernels of black walnuts. The metabolomics approach provides a simple and cost-effective tool for bioactive compound identification.

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Azelaic Acid Exerts Antileukemic Activity in Acute Myeloid Leukemia

Cited by 17 publications

References 23 publications

p53: key conductor of all anti-acne therapies

p53: key conductor of all anti-acne therapies

Mutational spectrum and associations with clinical features in patients with acute myeloid leukaemia based on next‑generation sequencing

Identifying Antibacterial Compounds in Black Walnuts (Juglans nigra) Using a Metabolomics Approach

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