Fraxetin Inhibits the Proliferation and Metastasis of Glioma Cells by Inactivating JAK2/STAT3 Signaling

Qu, Liangchen; Lin, Pan; Lin, Minjie; Ye, Shumin; Akuetteh, Percy David Papa; Zhu, Youyou

doi:10.1155/2021/5540139

Cited by 8 publications

(11 citation statements)

References 32 publications

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“…And these inflammatory factors act on the liver cell biofilms and damage the liver cells, thereby causing liver failure [ 21 , 22 ]. Meanwhile, according to the study, interleukins IL-10 and IL-6 can upregulate CD163 expression in monocytes [ 23 , 24 ]. Unlike cytokines, most proinflammatory factors such as IFN γ , LPS, and TNF- α can downregulate the expression of CD163 [ 25 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

[Retracted] Chinese Herb Jiedu Huayu Granules Inhibiting Immune and Inflammatory Response of Rats with Acute Liver Failure by Regulating the NF‐κB Signaling Pathway

Bai

Shi

et al. 2022

BioMed Research International

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Objective. To research the influence of Chinese medicine Jiedu Huayu granules (JDHY) on the immune response and inflammatory response of rats with acute liver failure (ALF) and investigate its related mechanism. Methods. Rats were randomly divided into 4 groups: control group ( n = 6 ) were injected with the same amount of normal saline; ALF group ( n = 10 ) were injected intraperitoneally with D-GaIN (700 mg/kg) and LPS (10 μg/kg); ALF+JDHY group ( n = 10 ) were given JDHY 57.55 g/kg/d by gavage for 7 days and injected intraperitoneally with D-GaIN/LPS after the last dose; and ALF+BAY group ( n = 10 ) were given BAY 10 mg/kg/d by gavage for 7 days and injected intraperitoneally with D-GaIN/LPS after the last dose. Changes in liver function and coagulation function were examined in rat serum; the pathological varieties of liver tissues were verified by HE staining; immunohistochemistry was utilized to determine the ratio of PCNA and F4/80 in liver tissues; the flow cytometry was applied to determine the ratio of CD4+/CD8+ cells in peripheral blood mononuclear cells (PBMCs); ELISA and qRT-PCR were utilized to check the level of IL-10, IL-6, IL-13, IL-1β, TNF-α, IFN-γ, and CD163 in serum and liver cells. Western blot was adopted to check the expression of apoptotic protein and expression and NF-κB pathway-related protein expression. Results. JDHY and BAY could decline the expression of AST, ALT, ALP, and TBiL in ALF rat serum significantly ( P < 0.01 ), increase PTA and PLT ( P < 0.01 ), and mitigate liver tissue damage. Besides, JDHY and BAY could reduce the apoptosis and improve the proliferation of the liver cells in rats with ALF; meanwhile, the ratio of CD4+ cells and F4/80 cells was reduced while CD8+ cells were increased ( P < 0.01 ). Further, JDHY and BAY could reduce the level of IFN-γ, IL-6, IL-1β, and TNF-α while increasing the level of IL-10 and IL-13 ( P < 0.01 ). Additionally, the expression of sCD163 in serum and CD163 expression in liver tissues increased ( P < 0.01 ). The result of western blot confirmed that JDHY could inhibit the phosphorylated expression of NF-κB, IKβα, and IKKβ in the ALF rat tissues. Conclusions. JDHY can upregulate the level of CD163/sCD163 by the NF-κB signaling pathway, thereby regulating immune response, inhibiting inflammatory response, and ultimately improving ALF in the rats.

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Section: Discussionmentioning

confidence: 99%

[Retracted] Chinese Herb Jiedu Huayu Granules Inhibiting Immune and Inflammatory Response of Rats with Acute Liver Failure by Regulating the NF‐κB Signaling Pathway

Bai

Shi

et al. 2022

BioMed Research International

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“…Fraxetin also inhibits MCF-7 breast cancer cells proliferation of and induces cell apoptosis [ 3 ]. A recent study reported that Fraxetin inhibits proliferation and metastasis of glioma cells by inactivating JAK2/STAT3 signaling [ 6 ]. Tumor invasion and metastasis remain the major causes of deaths in prostate cancer patients [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…Afterward, a crystal pipette tip was employed to create a linear gap between the cells. The cells were washed with phosphate buffer solution (PBS) three times before the addition of new serum-free medium containing a series concentration of Fraxetin (0, 10, 20, and 40 μM) for another 48 h [ 6 ]. Finally, images of the culture area were captured under a light microscope (magnification, x100; Olympus Corporation).…”

Section: Methodsmentioning

confidence: 99%

“…Modern pharmacological studies have supported that Fraxetin has various pharmacological properties, such as antibacterial and anti-inflammatory, inhibiting oxidative stress, neuroprotection, tumor suppression, and immunomodulation effects [ 1 ]. Accumulating studies have reported the anti-cancer effects of Fraxetin on a variety of tumors, such as liver cancer [ 2 ], breast cancer [ 3 ], colon adenocarcinoma [ 4 ], pancreatic cancer [ 5 ], and glioma [ 6 ]. These studies illustrated the powerful potential of Fraxetin in anti-cancer, but whether Fraxetin exhibited anti-cancer effect on prostate cancer remain to be clarified.…”

Section: Introductionmentioning

confidence: 99%

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Fraxetin down-regulates polo-like kinase 4 (PLK4) to inhibit proliferation, migration and invasion of prostate cancer cells through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway

Sun

Peng

2022

Bioengineered

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Fraxetin, a natural product isolated from herb Cortex Fraxini , has been demonstrated to exhibit anti-cancer effects on various cancers. The aim of this work is to investigate the anti-tumor effect of Fraxetin in prostate cancer and the potential mechanisms. In this study, the prostatic epithelial cell RWPE-1 and prostate cancer cell DU145 were exposed to Fraxetin (10, 20, 40, and 80 μM) to detect the changes in cell viability using cell counting kit-8 (CCK-8) assay. Fraxetin (10, 20, and 40 μM) was utilized to treat DU145 cell, then the changes in cell proliferation, apoptosis, migration, and invasion were assessed. Western blot assay was employed to detect the expression of proteins that participate in the above cellular processes as well as Polo-like kinase 4 (PLK4), phosphatidylinositol 3-kinase (PI3K). In addition to 40 μM Fraxetin treatment, DU145 cells were overexpressed with PLK4, and then the above experiments were repeated. Results revealed that Fraxetin markedly decreased DU145 cell viability, but didn’t affect the cell viability of RWPE-1. Fraxetin suppressed cell proliferation, migration, invasion, and induced apoptosis of DU145 cells in a concentration-dependent manner. Furthermore, the expression of PLK4 and phosphorylated PI3K and protein kinase B (Akt) were reduced upon Fraxetin treatment. Finally, PLK4 overexpression significantly reversed all the effects of Fraxetin on DU145 cells. Collectively, Fraxetin acted as a cancer suppressor in prostate cancer through inhibiting PLK4 expression thereby inactivating PI3K/Akt signaling.

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“…Yangyang Guo et al reported that FXT inhibited the development of pancreatic cancer by antagonizing STAT3 activation (Guo et al, 2021). Of note, Liangchen Qu et al found that FXT inhibits the proliferation and metastasis of glioma cells by inhibiting the JAK2/STAT3 signaling pathway (Qu et al, 2021). In addition, Ying Su et al found that JAK2 inhibitors and si‐STAT3 inhibited the level of miR‐21 in human renal cell carcinoma cells (Su et al, 2017), suggesting that FXT may inhibit the expression of miR‐21‐3p by inhibiting the JAK2/STAT3 signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Fraxetin exerts anticancer effect in glioma by suppressing MiR‐21‐3p

Yao

Pan

et al. 2021

Drug Development Research

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Fraxetin (FXT) exerts anticancer function in multiple cancers, but its function on glioma was ill‐defined. This article expounded the mechanism by which FXT exerts an anticancer effect in glioma. The effect of gradient concentration of FXT on the viability of glioma cell lines was determined by cell counting kit 8. Effects of FXT on proliferation, apoptosis, and cell cycle in glioma cell lines were determined by colony formation assay, flow cytometry, and Hoechst 33342 staining. Expressions of apoptosis‐related gene, cycle‐related gene, and glioma‐related miRNAs after FXT (25 and 50 μmol/L) treatment were determined by quantitative reverse transcription polymerase chain reaction and western blot as needed. After miR‐21‐3p overexpression, cell viability and apoptosis of glioma cell lines treated with FXT (50 μmol/L) were tested again. Although 1 μmol/L FXT had no significant effect on cell viability, 5, 10, 25, and 50 μmol/L FXT suppressed cell viability in a concentration‐dependent manner. FXT inhibited proliferation, promoted apoptosis, and induced cell cycle arrest in G0/G1 phase in glioma cell lines. These effects may be achieved by elevated expressions of Bax and cleaved caspase‐3 and diminished expressions of Bcl‐2, Bcl‐XL, cyclin E1, cyclin D1, and cyclin‐dependent kinase‐6. FXT attenuated the contents of miR‐21‐3p and miR‐455‐3p, and escalated the contents of miR‐124‐3p and miR‐7‐5p. The regulation of FXT on cell viability, proliferation and apoptosis was reversed by miR‐21‐3p overexpression. FXT suppressed the development of glioma cells by downregulating miR‐21‐3p.

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Fraxetin Inhibits the Proliferation and Metastasis of Glioma Cells by Inactivating JAK2/STAT3 Signaling

Cited by 8 publications

References 32 publications

[Retracted] Chinese Herb Jiedu Huayu Granules Inhibiting Immune and Inflammatory Response of Rats with Acute Liver Failure by Regulating the NF‐κB Signaling Pathway

[Retracted] Chinese Herb Jiedu Huayu Granules Inhibiting Immune and Inflammatory Response of Rats with Acute Liver Failure by Regulating the NF‐κB Signaling Pathway

Fraxetin down-regulates polo-like kinase 4 (PLK4) to inhibit proliferation, migration and invasion of prostate cancer cells through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway

Fraxetin exerts anticancer effect in glioma by suppressing MiR‐21‐3p

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