Vitamin E inhibits cyclosporin A-induced CTGF and TIMP-1 expression by repressing ROS-mediated activation of TGF-β/Smad signaling pathway in rat liver

Balah, Amany; Ezzat, Omnia; Akool, El-Sayed

doi:10.1016/j.intimp.2018.09.033

Cited by 45 publications

(26 citation statements)

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“…NRK-49F cells have been demonstrated to express CTGF, α-SMA, FN and Col III (6–9). Following treatment with different concentrations of MG132, the mRNA expression of CTGF, α-SMA, FN and Col III decreased compared with the control group, and exhibited a potential dose-dependent effect (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In a normal physiological environment, CTGF has been demonstrated to be mainly involved in angiogenesis and cell differentiation (8). It is worth noting that CTGF could mediate the process of tissue repair and fibrosis under pathological conditions (9). In the process of myocardial injury, repair and fibrosis, CTGF has been revealed to be a molecule that activates fibroblasts (10).…”

Section: Introductionmentioning

confidence: 99%

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Proteasome inhibitor MG132 inhibits the process of renal interstitial fibrosis

et al. 2019

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The proteasome inhibitor pathway serves a crucial role in cell cycle progression and apoptosis, and in the activation of transcription factors and cytokines in tumor cells. The aim of the current study was to investigate the effect of the proteasome inhibitor, MG132, on transforming growth factor (TGF)-β1-induced expression of extracellular matrix proteins in rat renal interstitial fibroblasts (NRK-49F cells) and to better elucidate the mechanism by which MG132 functions. The level of connective tissue growth factor (CTGF), α-smooth muscle actin (SMA), fibronectin (FN) and collagen type III (Col III) in the MG132-pretreated groups was significantly decreased compared with groups treated with TGF-β1 alone. MG132 significantly decreased mRNA and the protein levels of fibrosis-associated factors induced by TGF-β1 treatment. The MG132-pretreated groups exhibited lower phosphorylated-mothers against decapentaplegic homolog (p-Smad)2, p-Smad3 and FN protein expression compared with the groups treated with TGF-β1 alone. In conclusion, MG132 reduced mRNA and protein expression of fibrosis-associated factors. It can successfully inhibit the inflammatory reaction induced by TGF-β via the Smad signaling pathway. These results indicate that MG132 appears to have a potent effect in counteracting renal fibrosis. MG132 may be applied in the treatment of patients with chronic kidney disease.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Proteasome inhibitor MG132 inhibits the process of renal interstitial fibrosis

et al. 2019

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“…Western blot technique was applied to assess the potential effect of compound 11e on the expression of caspase‐9, caspase‐3, BAX, and Bcl‐2 as reported in Supplementary data 77–79 .…”

Section: Methodsmentioning

confidence: 99%

Discovery of new 3-methylquinoxalines as potential anti-cancer agents and apoptosis inducers targeting VEGFR-2: design, synthesis, and in silico studies

Alanazi

Elwan

Alsaif

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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There is an urgent need to design new anticancer agents that can prevent cancer cell proliferation even with minimal side effects. Accordingly, two new series of 3-methylquinoxalin-2(1 H )-one and 3-methylquinoxaline-2-thiol derivatives were designed to act as VEGFR-2 inhibitors. The designed derivatives were synthesised and evaluated in vitro as cytotoxic agents against two human cancer cell lines namely, HepG-2 and MCF-7. Also, the synthesised derivatives were assessed for their VEGFR-2inhibitory effect. The most promising member 11e were further investigated to reach a valuable insight about its apoptotic effect through cell cycle and apoptosis analyses. Moreover, deep investigations were carried out for compound 11e using western-plot analyses to detect its effect against some apoptotic and apoptotic parameters including caspase-9, caspase-3, BAX, and Bcl-2. Many in silico investigations including docking, ADMET, toxicity studies were performed to predict binding affinity, pharmacokinetic, drug likeness, and toxicity of the synthesised compounds. The results revealed that compounds 11e, 11g, 12e, 12g, and 12k exhibited promising cytotoxic activities (IC 50 range is 2.1 − 9.8 µM), comparing to sorafenib (IC 50 = 3.4 and 2.2 µM against MCF-7 and HepG2, respectively). Moreover, 11b, 11f, 11g, 12e, 12f, 12g, and 12k showed the highest VEGFR-2 inhibitory activities (IC 50 range is 2.9 − 5.4 µM), comparing to sorafenib (IC 50 = 3.07 nM). Additionally, compound 11e had good potential to arrest the HepG2 cell growth at G2/M phase and to induce apoptosis by 49.14% compared to the control cells (9.71%). As well, such compound showed a significant increase in the level of caspase-3 (2.34-fold), caspase-9 (2.34-fold), and BAX (3.14-fold), and a significant decrease in Bcl-2 level (3.13-fold). For in silico studies, the synthesised compounds showed binding mode similar to that of the reference compound (sorafenib).

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“…Western blot technique was performed for compound 23j to determine its effect against caspase3, caspase9, BAX, and Bcl-2 as described in Supplementary data 80–82 .…”

Section: Methodsmentioning

confidence: 99%

Discovery of new VEGFR-2 inhibitors based on bis([1, 2, 4]triazolo)[4,3-a:3',4'-c]quinoxaline derivatives as anticancer agents and apoptosis inducers

Alsaif

Taghour

Alanazi

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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Herein, a new wave of bis([1, 2, 4]triazolo)[4,3- a :3',4'- c ]quinoxaline derivatives have been successfully designed and synthesised. The synthesised derivatives were biologically investigated for their cytotoxic activities against HepG2 and MCF-7. Also, the tested compounds were further examined in vitro for their VEGFR-2 inhibitory activity. The most promising derivative 23j was further investigated for its apoptotic behaviour in HepG2 cell lines using flow cytometric and western-plot analyses. Additional in-silico studies were performed to predict how the synthesised compounds can bind to VEGFR-2 and to determine the drug-likeness profiling of these derivatives. The results revealed that compounds 23a , 23i , 23j , 23l , and 23n displayed the highest antiproliferative activities against the two cell lines with IC 50 values ranging from 6.4 to 19.4 µM. Furthermore, compounds 23a , 23d , 23h , 23i , 23j , 23l , 23 m , and 23n showed the highest VEGFR-2 inhibitory activities with IC 50 values ranging from 3.7 to 11.8 nM, comparing to sorafenib (IC 50 = 3.12 nM). Moreover, compound 23j arrested the HepG2 cell growth at the G2/M phase and induced apoptosis by 40.12% compared to the control cells (7.07%). As well, such compound showed a significant increase in the level of caspase-3 (1.36-fold), caspase-9 (2.80-fold), and BAX (1.65-fold), and exhibited a significant decrease in Bcl-2 level (2.63-fold).

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Vitamin E inhibits cyclosporin A-induced CTGF and TIMP-1 expression by repressing ROS-mediated activation of TGF-β/Smad signaling pathway in rat liver

Cited by 45 publications

References 46 publications

Proteasome inhibitor MG132 inhibits the process of renal interstitial fibrosis

Proteasome inhibitor MG132 inhibits the process of renal interstitial fibrosis

Discovery of new 3-methylquinoxalines as potential anti-cancer agents and apoptosis inducers targeting VEGFR-2: design, synthesis, and in silico studies

Discovery of new VEGFR-2 inhibitors based on bis([1, 2, 4]triazolo)[4,3-a:3',4'-c]quinoxaline derivatives as anticancer agents and apoptosis inducers

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