Looking for the best anti-colitis medicine: A comparative analysis of current and prospective compounds

Chumanevich, Anastasiya A.; Chaparala, Anusha; Witalison, Erin E.; Tashkandi, Hossam; Hofseth, Anne B.; Lane, Corey; Peña, Edsel A.; Liu, Piaomu; Pittman, Doug L.; Nagarkatti, Mitzi; Hofseth, Lorne J.; Chumanevich, Alexander A.

doi:10.18632/oncotarget.13894

Cited by 13 publications

(12 citation statements)

References 45 publications

(54 reference statements)

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“…The negative control was carried out without primary antibody incubation. Intensity and degree of staining for YAP1 were evaluated independently by two blinded investigators (AC, ZM) as described previously [55]. For each tissue section the percentage of cells with nuclear YAP1 staining was calculated in five randomly chosen areas per sample by each of two independent researchers (AC, ZM).…”

Section: Histology and Immunohistochemical Stainingmentioning

confidence: 99%

Mediator kinase CDK8/CDK19 drives YAP1-dependent BMP4-induced EMT in cancer

et al. 2018

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CDK8 is a transcription-regulating kinase that controls TGF-β/BMP-responsive SMAD transcriptional activation and turnover through YAP1 recruitment. However, how the CDK8/YAP1 pathway influences SMAD1 response in cancer remains unclear. Here we report that SMAD1-driven epithelial-to-mesenchymal transition (EMT) is critically dependent on matrix rigidity and YAP1 in a wide spectrum of cancer models. We find that both genetic and pharmacological inhibition of CDK8 and its homologous twin kinase CDK19 leads to abrogation of BMP-induced EMT. Notably, selectively blocking CDK8/19 specifically abrogates tumor cell invasion, changes in EMT-associated transcription factors, E-cadherin expression and YAP nuclear localization both in vitro and in vivo in a murine syngeneic EMT model. Furthermore, RNA-seq meta-analysis reveals a direct correlation between CDK8 and EMT-associated transcription factors in patients. Our findings demonstrate that CDK8, an emerging therapeutic target, coordinates growth factor and mechanical cues during EMT and invasion.

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Section: Histology and Immunohistochemical Stainingmentioning

confidence: 99%

Mediator kinase CDK8/CDK19 drives YAP1-dependent BMP4-induced EMT in cancer

et al. 2018

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“…The predominant drug-based therapies used in UC management, such as aminosalicylic acid, corticosteroids, 6-mercaptopurine, azathioprine and cyclosporine give rise to a range of debilitating side effects at various sites, such as skin, eyes and muscle [ 19 , 20 ]. These therapeutic agents also induce bone marrow depletion and disorders in the lungs, liver and pancreas [ 21 – 23 ]. Additionally, these treatments are not only non-selective, but also impair lifestyle due to repeated use for protracted periods of time [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

“…More sophisticated approaches based on novel and potent therapeutic agents, such as monoclonal antibodies, protease inhibitors and anti-TNF-α compounds, are also used in UC [ 27 , 28 ] but their use has limitations due to side effects linked to liver damage, heart disease, infection, skin disease and degenerative disorders [ 25 ]. Arguably, the use of biomolecular drug substances offer few advantages, yet inflict toxicity, non-selectivity and a cost burden on patients [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Albumin nano-encapsulation of caffeic acid phenethyl ester and piceatannol potentiated its ability to modulate HIF and NF-kB pathways and improves therapeutic outcome in experimental colitis

Tambuwala

Khan

Thompson

et al. 2018

Drug Deliv. and Transl. Res.

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Hypoxia inducible factor and nuclear factor-kappa beta pathways have been proposed as therapeutic targets for several inflammatory diseases. Caffeic acid phenethyl ester (CAPE) and piceatannol (PIC) are natural anti-inflammatory compounds; however, poor bioavailability and limited understanding of biomolecular mechanistic limits its clinical use. The aims of this study are to enhance bioavailability and investigate their impact on nuclear p65 and HIF-1α for the first time in experimental colitis.Dextran sulphate sodium was used to induce colitis in mice and effect of either free CAPE/PIC or CAPE/PIC loaded albumin nanoparticles treatment was observed on disease development and levels of cellular p65 and HIF-1α.Our results indicate that albumin nano-encapsulation of CAPE/PIC not only enhances its anti-inflammatory potential but also potentiates its ability to effectively modulate inflammation related biomolecular pathways. Hence, combining nanotechnology with natural compounds could result in development of new therapeutic options for IBD.Electronic supplementary materialThe online version of this article (10.1007/s13346-018-00597-9) contains supplementary material, which is available to authorized users.

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“…Since 4-HNE is known to activate Nrf2 [ 29 ] and is also a marker of inflammation, we probed for this endpoint. Figure 2 A shows induced expression of 4-HNE in the DSS-treated group and its suppression when mice also consumed AG, HAG or PA. We have previously shown that AG and HAG suppress colitis in mice [ 18 , 19 , 21 , 22 , 30 ]. Consistent with our previous findings, AG, HAG, and now PA suppress colitis in DSS-treated mice ( Figure 2 A).…”

Section: Resultsmentioning

confidence: 99%

Molecules from American Ginseng Suppress Colitis through Nuclear Factor Erythroid-2-Related Factor 2

et al. 2020

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Ulcerative colitis (UC) is a chronic inflammatory bowel disease that affects millions of people worldwide and increases the risk of colorectal cancer (CRC) development. We have previously shown that American ginseng (AG) can treat colitis and prevent colon cancer in mice. We further fractionated AG and identified the most potent fraction, hexane fraction (HAG), and the most potent compound in this fraction, panaxynol (PA). Because (1) oxidative stress plays a significant role in the pathogenesis of colitis and associated CRC and (2) nuclear factor erythroid-2-related factor 2 (Nrf2) is the master regulator of antioxidant responses, we examined the role of Nrf2 as a mechanism by which AG suppresses colitis. Through a series of in vitro and in vivo Nrf2 knockout mouse experiments, we found that AG and its components activate the Nrf2 pathway and decrease the oxidative stress in macrophages (mΦ) and colon epithelial cells in vitro. Consistent with these in vitro results, the Nrf2 pathway is activated by AG and its components in vivo, and Nrf2-/- mice are resistant to the suppressive effects of AG, HAG and PA on colitis. Results from this study establish Nrf2 as a mediator of AG and its components in the treatment of colitis.

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Looking for the best anti-colitis medicine: A comparative analysis of current and prospective compounds

Cited by 13 publications

References 45 publications

Mediator kinase CDK8/CDK19 drives YAP1-dependent BMP4-induced EMT in cancer

Mediator kinase CDK8/CDK19 drives YAP1-dependent BMP4-induced EMT in cancer

Albumin nano-encapsulation of caffeic acid phenethyl ester and piceatannol potentiated its ability to modulate HIF and NF-kB pathways and improves therapeutic outcome in experimental colitis

Molecules from American Ginseng Suppress Colitis through Nuclear Factor Erythroid-2-Related Factor 2

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