scholarly journals The synthetic triterpenoids CDDO-TFEA and CDDO-Me, but not CDDO, are potent BACH1 inhibitors

2021 ◽  
Author(s):  
Laura Casares ◽  
Rita Moreno ◽  
Maureen Higgins ◽  
Sharada Dayalan Naidu ◽  
Graham Neill ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Chronic Conditions ◽  
Cancer Metastasis ◽  
Antioxidant Properties ◽  
Heme Oxygenase 1 ◽  
Therapeutic Uses ◽  
Nuclear Levels ◽  
Therapeutic Activities ◽  
Derivatives Of ◽  
Therapeutic Profile

The transcription factor BACH1 is a potential target against a variety of chronic conditions linked to oxidative stress and inflammation, and formation of cancer metastasis. However, only a few BACH1 degraders/inhibitors have been described. BACH1 is a transcriptional repressor of heme oxygenase 1 (HMOX1), which is positively regulated by transcription factor NRF2 and is highly inducible by derivatives of the synthetic oleanane triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO). Most of the therapeutic activities of these compounds are due to their anti-inflammatory and antioxidant properties, which are widely attributed to their ability to activate NRF2. However, with such a broad range of action, these drugs may have other molecular targets that have not been fully identified and could also be of importance for their therapeutic profile. Herein we identified BACH1 as a target of CDDO-derivatives, but not CDDO. While both CDDO and CDDO-derivatives activate NRF2 similarly, only CDDO-derivatives inhibit BACH1, which explains the much higher potency of CDDO-derivatives as HMOX1 inducers compared with unmodified CDDO. Notably, we demonstrate that CDDO-derivatives inhibit BACH1 via a novel mechanism that reduces BACH1 nuclear levels while accumulating its cytoplasmic form. Altogether, our study identifies CDDO-derivatives as dual KEAP1/BACH1 inhibitors, providing a rationale for further therapeutic uses of these drugs

scholarly journals Avocado-Derived Biomass: Chemical Composition and Antioxidant Potential

Proceedings ◽  
2020 ◽  
Vol 70 (1) ◽  
pp. 100
Author(s):  
Minerva C. García-Vargas ◽  
María del Mar Contreras ◽  
Irene Gómez-Cruz ◽  
Juan Miguel Romero-García ◽  
Eulogio Castro
Keyword(s):  
Chemical Composition ◽  
Phenolic Content ◽  
Antioxidant Properties ◽  
Total Phenolic ◽  
Nutritional Properties ◽  
Aqueous Fraction ◽  
Extraction Solvent ◽  
Main Components ◽  
A Minor ◽  
Derivatives Of

Avocado has become fashionable due to its great organoleptic and nutritional properties. It is consumed as a fresh product and it is also processed to obtain salad oil and guacamole. In all cases, the only usable portion is the pulp. Therefore, to be a more sustainable and profitable agribusiness, it is important to recognize which compounds from the peel and the stone waste can be converted into valuable bio-products. Therefore, their chemical composition was determined according to the National Renewable Energy Laboratory, the total phenolic content by the Folin-Ciocalteu method and the antioxidant properties by the FRAP and TEAC assays. The main components of the peel and stone were acid-insoluble lignin (35.0% and 15.3%, respectively), polymeric sugars (23.6% and 43.9%, respectively), and the aqueous extractives (15.5% and 16.9%, respectively). Both biomasses contain lipids and protein, but a minor proportion (<6%). The valorization of lignin and sugars is of interest given the high content; stones are a rich source of glucose (93.2% of the polymeric fraction), which could be used to obtain biofuels or derivatives of interest. The extractive fraction of the peel contained the highest number of phenolic compounds (4.7 g/100 g biomass), mainly concentrated in the aqueous fraction (i.e., 87%) compared to the ethanol one, which was subsequently extracted. It correlated with major antioxidant activity and, therefore, the peel can be applied to obtain antioxidants and water can be used as an environmentally friendly extraction solvent.

scholarly journals Interplay Between Heme Oxygenase-1 and the Multifunctional Transcription Factor Yin Yang 1 in the Inhibition of Intimal Hyperplasia

2010 ◽  
Vol 107 (12) ◽  
pp. 1490-1497 ◽  
Author(s):  
Konstanze Beck ◽  
Ben J. Wu ◽  
Jun Ni ◽  
Fernando S. Santiago ◽  
Kristine P. Malabanan ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Heme Oxygenase ◽  
Intimal Hyperplasia ◽  
Heme Oxygenase 1 ◽  
Yin Yang 1 ◽  
Yin Yang ◽  
Multifunctional Transcription Factor

MP61-19 A NOVEL ROLE OF THE TRANSCRIPTION FACTOR TCF21 AS A SUPPRESSOR OF BLADDER CANCER METASTASIS

2014 ◽  
Vol 191 (4S) ◽  
Author(s):  
Sima Porten ◽  
Beat Roth ◽  
Jonathan Melquist ◽  
Woonyoung Choi ◽  
Shanna Pretzsch ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Transcription Factor ◽  
Cancer Metastasis

scholarly journals Anti-Inflammatory and Antioxidant Effects of Soroseris hirsuta Extract by regulating iNOS/NF-κB and NRF2/HO-1 Pathways in Murine Macrophage RAW 264.7 Cells

2021 ◽  
Vol 11 (10) ◽  
pp. 4711
Author(s):  
Woo Jin Lee ◽  
Wan Yi Li ◽  
Sang Woo Lee ◽  
Sung Keun Jung
Keyword(s):  
Nitric Oxide ◽  
Nuclear Translocation ◽  
Antioxidant Properties ◽  
Raw 264.7 Cells ◽  
Heme Oxygenase 1 ◽  
Raw 264.7 ◽  
Related Factor ◽  
Iκb Kinase ◽  
Anti Inflammatory ◽  
Antioxidant Effects

Until now, the physiological effects of Soroseris hirsuta were primarily unknown. Here we have evaluated the anti-inflammatory and antioxidant effects of Soroseris hirsuta extract (SHE) on lipopolysaccharide (LPS)-activated murine macrophages RAW 264.7 cells. SHE inhibited nitric oxide expression and inducible nitric oxide synthase expression in RAW 264.7 cells treated with LPS. Moreover, SHE suppressed LPS-induced phosphorylation of IκB kinase, inhibitor of kappa B, p65, p38, and c-JUN N-terminal kinase. Western blot and immunofluorescence analyses showed that SHE suppressed p65 nuclear translocation induced by LPS. Furthermore, SHE inhibited the reactive oxygen species in LPS-treated RAW 264.7 cells. SHE significantly increased heme oxygenase-1 expression and the nuclear translocation of nuclear factor erythroid 2-related factor 2. SHE suppressed LPS-induced interleukin-1β mRNA expression in RAW 264.7 cells. Thus, SHE is a promising nutraceutical as it displays anti-inflammatory and antioxidant properties.

scholarly journals The Protective Role of Resveratrol against Arsenic Trioxide-Induced Cardiotoxicity

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Weiqian Zhang ◽  
Changming Guo ◽  
Ruifeng Gao ◽  
Ming Ge ◽  
Yanzhu Zhu ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Cardiac Dysfunction ◽  
Oxidative Dna Damage ◽  
Antioxidant Properties ◽  
Reactive Oxygen Species Generation ◽  
Protective Role ◽  
Natural Food ◽  
Heme Oxygenase 1 ◽  
Related Factor

Arsenic trioxide (As2O3) shows substantial anticancer activity in patients with acute promyelocytic leukemia (APL). Unfortunately, limiting the application of this effective agent to APL patients is severe cardiotoxicity. Resveratrol, the natural food-derived polyphenolic compound, is well known for its antioxidant properties and protects the cardiovascular system. But the potential role of resveratrol against As2O3in heart via nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) is unclear. The present study evaluated the effects of pretreatment with resveratrol and As2O3on oxidative stress and cardiac dysfunction in rat. In the present study, resveratrol decreased As2O3-induced reactive oxygen species generation, oxidative DNA damage, and pathological alterations. In addition, cardiac dysfunction parameters, intracellular calcium and arsenic accumulation, glutathione redox ratio, and cAMP deficiency levels were observed in As2O3-treated rats; these changes were attenuated by resveratrol. Furthermore, resveratrol significantly prohibited the downregulation of both Nrf2 and HO-1 gene expressions that were downregulated by As2O3, whereas resveratrol did not alter As2O3-induced nitric oxide formation. Thus, the protective role of resveratrol against As2O3-induced cardiotoxicity is implemented by the maintenance of redox homeostasis (Nrf2-HO-1 pathway) and facilitating arsenic efflux. Our findings suggest coadministration with resveratrol, and As2O3might provide a novel therapeutic strategy for APL.

Therapeutic Journey of Andrographis paniculata (Burm.f.) Nees from Natural to Synthetic and Nanoformulations

2021 ◽  
Vol 21 ◽  
Author(s):  
Sharuti Mehta ◽  
Anil Kumar Sharma ◽  
Rajesh K. Singh
Keyword(s):  
Biological Activities ◽  
Andrographis Paniculata ◽  
Herbaceous Plant ◽  
Target Tissue ◽  
Active Components ◽  
Essential Information ◽  
Compound Plant ◽  
Therapeutic Activities ◽  
Synthetic Derivatives ◽  
Derivatives Of

: Andrographis paniculata (Burm.f.) Nees (Acanthaceae) is a herbaceous plant and commonly called 'King of Bitters'. It has gained attraction as a potential hepatoprotective agent and a natural molecule with various biological activities viz. anticancer, immunomodulatory, anti-inflammatory, antibacterial, neuroprotective, and so on. The andrographolide is one of the main diterpenoids responsible for the drug's bitter taste and various therapeutic activities. The poor cellular permeability, solubility and short biological half-life of its pure components limit its distribution to the target tissue. To conquer this obstacle, various researchers worldwide have been working on designing the synthetic derivatives of its active components and nanoformulations to improve the drug's efficiency and selectivity to develop more active leads for biomedical applications. This article discussed the recent research on synthetic derivatives, including their possible therapeutic applications and structure-activity relationship (SAR). Additionally, this article also presents the essential information concerning the various nanoformulations developed to increase the delivery of pure compound/plant extract to the target site, thereby improving the drug's efficacy for multiple ailments.

Induction of HOXA3 by PRRSV inhibits IFN-I response through negatively regulation of HO-1 transcription

2021 ◽  
Author(s):  
Yingtong Feng ◽  
Xuyang Guo ◽  
Hong Tian ◽  
Yuan He ◽  
Yang Li ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Gene Transcription ◽  
Immune Evasion ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Host Cells ◽  
Type I Interferons ◽  
Economic Losses ◽  
Heme Oxygenase 1 ◽  
Type I

Type I interferons (IFN-I) play a key role in the host defense against virus infection, but porcine reproductive and respiratory syndrome virus (PRRSV) infection does not effectively activate IFN-I response, and the underlying molecular mechanisms are poorly characterized. In this study, a novel transcription factor of the heme oxygenase-1 (HO-1) gene, homeobox A3 (HOXA3), was screened and identified. Here, we found that HOXA3 was significantly increased during PRRSV infection. We demonstrated that HOXA3 promotes PRRSV replication by negatively regulating the HO-1 gene transcription, which is achieved by regulating type I interferons (IFN-I) production. A detailed analysis showed that PRRSV exploits HOXA3 to suppress beta interferon (IFN-β) and IFN-stimulated gene (ISG) expression in host cells. We also provide direct evidence that the activation of IFN-I by HO-1 depends on its interaction with IRF3. Then we further proved that deficiency of HOXA3 promoted the HO-1-IRF3 interaction, and subsequently enhanced IRF3 phosphorylation and nuclear translocation in PRRSV-infected cells. These data suggest that PRRSV uses HOXA3 to negatively regulate the transcription of the HO-1 gene to suppress the IFN-I response for immune evasion. IMPORTANCE Porcine reproductive and respiratory syndrome (PRRS), caused by PRRSV, leads the pork industry worldwide to significant economic losses. HOXA3 is generally considered to be an important molecule in the process of body development and cell differentiation. Here, we found a novel transcription factor of the HO-1 gene, HOXA3, can negatively regulate the transcription of the HO-1 gene and play an important role in the suppression of IFN-I response by PRRSV. PRRSV induces the upregulation of HOXA3, which can negatively regulate HO-1 gene transcription, thereby weakening the interaction between HO-1 and IRF3 for inhibiting the type I IFN response. This study extends the function of HOXA3 to the virus field for the first time and provides new insights into PRRSV immune evasion mechanism.

scholarly journals EMT cells increase breast cancer metastasis via paracrine GLI activation in neighbouring tumour cells

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Deepika Neelakantan ◽  
Hengbo Zhou ◽  
Michael U. J. Oliphant ◽  
Xiaomei Zhang ◽  
Lukas M. Simon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Tumour Cells ◽  
Human Breast ◽  
Breast Tumours ◽  
Cancer Models ◽  
Pdx Models

Abstract Recent fate-mapping studies concluded that EMT is not required for metastasis of carcinomas. Here we challenge this conclusion by showing that these studies failed to account for possible crosstalk between EMT and non-EMT cells that promotes dissemination of non-EMT cells. In breast cancer models, EMT cells induce increased metastasis of weakly metastatic, non-EMT tumour cells in a paracrine manner, in part by non-cell autonomous activation of the GLI transcription factor. Treatment with GANT61, a GLI1/2 inhibitor, but not with IPI 926, a Smoothened inhibitor, blocks this effect and inhibits growth in PDX models. In human breast tumours, the EMT-transcription factors strongly correlate with activated Hedgehog/GLI signalling but not with the Hh ligands. Our findings indicate that EMT contributes to metastasis via non-cell autonomous effects that activate the Hh pathway. Although all Hh inhibitors may act against tumours with canonical Hh/GLI signalling, only GLI inhibitors would act against non-canonical EMT-induced GLI activation.

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