Cucurbitacin E inhibits TNF-α-induced inflammatory cytokine production in human synoviocyte MH7A cells via suppression of PI3K/Akt/NF-κB pathways

Jia, Qiang; Cheng, Wenxiang; Yue, Ye; Hu, Yipping; Zhang, Jian; Pan, Xiaohua; Xu, Zuojun; Zhang, Peng

doi:10.1016/j.intimp.2015.08.026

Cited by 52 publications

(45 citation statements)

References 34 publications

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“…However, it is unknown whether PI3K/AKT/mTOR signalling pathway mediated the anti-cancer effect of CuE. Recently, Jia et al [35] reported that CuE exerted its anti-inflammatory properties in human synoviocyte MH7A cells via modulation of PI3K/Akt/NF-κB pathway. In the present study, to understand the mechanism by which CuE can lead to cell growth, we have measured p-AKT, p-p70S6K, p-mTOR and p-4EBP1.…”

Section: Discussionmentioning

confidence: 99%

Cucurbitacin E inhibits osteosarcoma cells proliferation and invasion through attenuation of PI3K/AKT/mTOR signalling pathway

Wang

et al. 2016

Bioscience Reports

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Cucurbitacin E (CuE), a potent member of triterpenoid family isolated from plants, has been confirmed as an antitumour agent by inhibiting proliferation, migration and metastasis in diverse cancer. However, the effects and mechanisms of CuE on osteosarcoma (OS) have not been well understood. The present study aimed to test whether CuE could inhibit growth and invasion of OS cells and reveal its underlying molecular mechanism. After various concentrations of CuE treatment, the anti-proliferative effect of CuE was assessed using the cell counting Kit-8 assay. Flow cytometry analysis was employed to measure apoptosis of OS cells. Cell cycle distribution was analysed by propidium iodide staining. Transwell assay was performed to evaluate the effect of CuE on invasion potential of OS cells. The protein levels were measured by western blot. In addition, the potency of CuE on OS cells growth inhibition was assessed in vivo. Our results showed that CuE inhibited cell growth and invasion, induced a cell cycle arrest and triggered apoptosis and modulated the expression of cell growth, cell cycle and cell apoptosis regulators. Moreover, CuE inhibited the PI3K/Akt/mTOR pathway and epithelial–mesenchymal transition (EMT), which suppressed the invasion and metastasis of OS. In addition, we also found that CuE inhibited OS cell growth in vivo. Taken together, our study demonstrated that CuE could inhibit OS tumour growth and invasion through inhibiting the PI3K/Akt/mTOR signalling pathway. Our findings suggest that CuE can be considered to be a promising anti-cancer agent for OS.

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Section: Discussionmentioning

confidence: 99%

Cucurbitacin E inhibits osteosarcoma cells proliferation and invasion through attenuation of PI3K/AKT/mTOR signalling pathway

Wang

et al. 2016

Bioscience Reports

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“…In the present investigation, we targeted fat tissue biology and dysfunction to treat metabolic syndrome. Accumulating evidence indicates anti-proliferative, anti-inflammatory and autophagic properties of Cucs and CuE in particular [12, 34, 35]. However, role of cucrbitacins in adipose tissue biology is poorly defined [16].…”

Section: Discussionmentioning

confidence: 99%

Cucurbitacin E reduces obesity and related metabolic dysfunction in mice by targeting JAK-STAT5 signaling pathway

et al. 2017

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Several members of cucurbitaceae family have been reported to regulate growth of cancer by interfering with STAT3 signaling. In the present study, we investigated the unique role and molecular mechanism of cucurbitacins (Cucs) in reducing symptoms of metabolic syndrome in mice. Cucurbitacin E (CuE) was found to reduce adipogenesis in murine adipocytes. CuE treatment diminished hypertrophy of adipocytes, visceral obesity and lipogenesis gene expression in diet induced mice model of metabolic syndrome (MetS). CuE also ameliorated adipose tissue dysfunction by reducing hyperleptinemia and TNF-alpha levels and enhancing hypoadiponectinemia. Results show that CuE mediated these effects by attenuating Jenus kinase- Signal transducer and activator of transcription 5 (JAK- STAT5) signaling in visceral fat tissue. As a result, CuE treatment also reduced PPAR gamma expression. Glucose uptake enhanced in adipocytes after stimulation with CuE and insulin resistance diminished in mice treated with CuE, as reflected by reduced glucose intolerance and glucose stimulated insulin secretion. CuE restored insulin sensitivity indirectly by inhibiting JAK phosphorylation and improving AMPK activity. Consequently, insulin signaling was up-regulated in mice muscle. As CuE positively regulated adipose tissue function and suppressed visceral obesity, dyslipedemia, hyperglycemia and insulin resistance in mice model of MetS, we suggest that CuE can be used as novel approach to treat metabolic diseases.

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“…It has also been shown that the PI3K/AKT signaling pathway is involved in the pathogenesis of inflammation [16]. Therefore, modulation of the PI3K/AKT signaling pathway may yield therapeutic benefits for RA [17]. In our study, we aim to explore the effects of miR-126 on the proliferation and apoptosis of RASFs by targeting PIK3R2 and regulating the PI3K-AKT signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-126 affects rheumatoid arthritis synovial fibroblast proliferation and apoptosis by targeting PIK3R2 and regulating PI3K-AKT signal pathway

Yuan

Deng

et al. 2016

Oncotarget

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Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and destruction of the joints as well as an increased risk of cardiovascular disease. RA synovial fibroblasts (RASFs) are involved in the progression of RA and release pro-inflammatory cytokines. On the other hand, microRNAs (miRs) may help control the inflammatory response of immune and non-immune cells. Therefore, our study used lentiviral expression vectors to test the effects of miR-126 overexpression on RASF proliferation and apoptosis. Luciferase experiments verified the targeting relationship between miR-126 and PIK3R2 gene. The co-transfection of anti-miR-126 and PIK3R2 siRNA to RASFs were used to identify whether PIK3R2 was directly involved in proliferation and apoptosis of miR-126-induced RASFs. Real-time polymerase chain reaction (PCR) was used to detect miR-126 and PIK3R2 expressions. MTT assay was used to detect cell proliferation. Flow cytometry was used to detect cell apoptosis and cell cycle. Western blotting was used to detect PIK3R2, PI3K, AKT and p-AKT proteins. After Lv-miR-126 infected RASFs, the relative expression of miR-126 was significantly enhanced. MiR-126 promoted RASF proliferation and inhibited apoptosis. Levels of PIK3R2 decreased while total PI3K and p-AKT levels increased in RASFs overexpressing miR-126. Co-transfection of anti-miR-126 and PIK3R2 siRNA also increased PI3K and p-AKT levels as well as RASF proliferation and reduced apoptosis, as compared to anti-miR-126 treatment alone. Finally, luciferase reporter assays showed that miR-126 targeted PIK3R2. Our data indicate that miR-126 overexpression in RASFs inhibits PIK3R2 expression and promotes proliferation while inhibiting apoptosis. This suggests inhibiting miR-126 may yield therapeutic benefits in the treatment of RA.

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Cucurbitacin E inhibits TNF-α-induced inflammatory cytokine production in human synoviocyte MH7A cells via suppression of PI3K/Akt/NF-κB pathways

Cited by 52 publications

References 34 publications

Cucurbitacin E inhibits osteosarcoma cells proliferation and invasion through attenuation of PI3K/AKT/mTOR signalling pathway

Cucurbitacin E inhibits osteosarcoma cells proliferation and invasion through attenuation of PI3K/AKT/mTOR signalling pathway

Cucurbitacin E reduces obesity and related metabolic dysfunction in mice by targeting JAK-STAT5 signaling pathway

MicroRNA-126 affects rheumatoid arthritis synovial fibroblast proliferation and apoptosis by targeting PIK3R2 and regulating PI3K-AKT signal pathway

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