Inhibition of STAT3 phosphorylation by sulforaphane reduces adhesion molecule expression in vascular endothelial cell

Cho, Young S.; Kim, Chan H.; Ha, Tae Sun; Ahn, Hee Yul

doi:10.1139/cjpp-2015-0150

Cited by 16 publications

(18 citation statements)

References 21 publications

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“…CST, a natural product isolated from Salvia miltiorrhiza Bunge, can significantly inhibit the STAT3 Tyr705 phosphorylation and the dimerization of STAT3 (40). Stattic can inhibit STAT3 Tyr705 and STAT3 Ser727 phosphorylation (41). When STAT is phosphorylated and forms dimerization, it can translocate into the nucleus and become a transcription factor.…”

Section: Discussionmentioning

confidence: 99%

FGFR2/STAT3 Signaling Pathway Involves in the Development of MMTV-Related Spontaneous Breast Cancer in TA2 Mice

Zhao

et al. 2020

Front. Oncol.

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The Tientsin Albino 2 (TA2) mouse has a high incidence of spontaneous breast cancer (SBC) in the absence of external inducers or carcinogens. The initiation of SBC is related to mouse mammary tumor virus (MMTV) infection and pregnancy. Pathologic analysis showed that breast cancer cells in TA2 mice are triple negative. Our previous study confirmed that fibroblast growth factor receptor 2 (FGFR2) expression increased in SBC tissue compared to that in their corresponding normal breast tissues of TA2 mice. The present study focused on the function of the FGFR2/STAT3 signaling pathway in the initiation of SBC. In this study, the expression of FGF3, FGFR2, STAT3, p-STAT3 Tyr705 , and p-STAT3 Ser727 was detected in serum and normal mammary gland tissues of TA2 mice with different number of pregnancies and SBC. The proliferation, invasiveness, and migration abilities of MA-891 cells from TA2 SBC were compared before and after cryptotanshinone and Stattic treatment. Transient siRNA transfection was used to detect the invasiveness, and migration abilities to avoid the off-targets effects. Downstream protein expression of STAT3 was also detected in MA-891 cells and TA2 xenografts from MA-891 inoculation. In addition, STAT3 expression was analyzed in 139 cases of human breast cancer including 117 cases of non-triple negative breast cancer (non-TNBC) (group I) and 22 cases of triple-negative breast cancer (TNBC) (group II). Results of our study confirmed that MMTV-LTR amplification, and FGFR2, p-STAT3 Tyr705 , p-STAT3 Ser727 expression increased with the number of pregnancies in the breast tissue of TA2 mice and were the highest in SBC. Serum FGF3 expression of SBC was higher than it of TA2 mice with different number of pregnancies. After STAT3 was inhibited, the abilities of proliferation, invasiveness, and migration in MA-891 decreased and the expression levels of STAT3, p-STAT3 Ser727 , p-STAT3 Tyr705 , Bcl2, cyclin D1, and c-myc in MA-891 and animal xenografts were also down-regulated. In human breast cancer, STAT3 expression was significantly higher in TNBC than that in non-TNBC. Our results showed that the FGFR2/STAT3 signaling pathway may be related to SBC initiation in TA2 mice. Inhibition of STAT3 can decrease proliferation, invasiveness, and migration in MA-891 cells and the growth of TA2 xenografts.

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Section: Discussionmentioning

confidence: 99%

FGFR2/STAT3 Signaling Pathway Involves in the Development of MMTV-Related Spontaneous Breast Cancer in TA2 Mice

Zhao

et al. 2020

Front. Oncol.

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“…Recently, studies have shown that LPS induces upregulation of cell adhesion molecules including ICAM-1, VCAM-1, and E-selectin in brain endothelial cells, indicating the mechanism underlying inflammation [ 32 , 33 ]. Consistent with these reports, our study showed that LPS increased the levels of cell adhesion molecules such as ICAM-1, VCAM-1, and E-selectin in CMECs.…”

Section: Discussionmentioning

confidence: 99%

Chrysin Attenuates VCAM-1 Expression and Monocyte Adhesion in Lipopolysaccharide-Stimulated Brain Endothelial Cells by Preventing NF-κB Signaling

Lee

2017

IJMS

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Adhesion of leukocytes to endothelial cells plays an important role in neuroinflammation. Therefore, suppression of the expression of adhesion molecules in brain endothelial cells may inhibit neuroinflammation. Chrysin (5,7-dihydroxyflavone) is a flavonoid component of propolis, blue passion flowers, and fruits. In the present study, we examined the effects of chrysin on lipopolysaccharide (LPS)-induced expression of vascular cell adhesion molecule-1 (VCAM-1) in mouse cerebral vascular endothelial (bEnd.3) cells. In bEnd.3 cells, LPS increased mRNA expression of VCAM-1 in a time-dependent manner, and chrysin significantly decreased LPS-induced mRNA expression of VCAM-1. Chrysin also reduced VCAM-1 protein expression in a concentration-dependent manner. Furthermore, chrysin blocked adhesion of monocytes to bEnd.3 cells exposed to LPS. Nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase, which are all activated by LPS, were significantly inhibited by chrysin. These results indicate that chrysin inhibits the expression of VCAM-1 in brain endothelial cells by inhibiting NF-κB translocation and MAPK signaling, resulting in the attenuation of leukocyte adhesion to endothelial cells. The anti-inflammatory effects of chrysin suggest a possible therapeutic application of this agent to neurodegenerative diseases, such as multiple sclerosis, septic encephalopathy, and allergic encephalomyelitis.

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“…5). The CRP, IL-1β, and ICAM-1 genes play key roles in inflammatory diseases via IL-6-induced STAT3 activation [30,31] and promote the recruitment and activation of inflammatory cells such as leukocytes [32,33]. Proteins that are suppressors of cytokine signaling (SOCS) are negative feedback regulators on the JAK/STAT3 pathway through the inhibition of JAKs activity [34].…”

Section: Resultsmentioning

confidence: 99%

Diarylheptanoids from Curcuma phaeocaulis Suppress IL-6-Induced STAT3 Activation

et al. 2018

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Three undescribed diarylheptanoids (3: -5: ) and six known curcuminoids (1, 2: , and 6: -9: ) were obtained from the ethyl acetate-soluble fraction of an ethanolic extract of . Their chemical structures and absolute configurations were elucidated by high-resolution electrospray ionization mass spectrometry, nuclear magnetic resonance spectroscopy, circular dichroism spectroscopy, and the modified Mosher's method. Previous studies constructed Hep3B cells stably transfected with pSTAT3-Luc plasmid containing STAT3 binding site to discover STAT3 inhibitors from natural products. The STAT3 inhibitory activities of all isolates were measured in transfected Hep3B cells after treatment with IL-6. Compound 5: ((5)-1,7-Bis(3,4-dimethoxyphenyl)-3-methoxy-1-hepten-5-ol), demethoxycurcumin (7: ), and curcumin (8: ) exhibited significant inhibitory activity (IC values: 11.1, 1.9, and 1.6 µM, respectively). Furthermore, IL-6-induced phosphorylation of STAT3, and the mRNA expression levels of inflammation-related genes such as CRP, IL-1β, ICAM-1, and SOCS3 were significantly reduced by exposure to compound 5: . These data suggested that the inhibitory activity of 5: is associated with the suppression of STAT3 phosphorylation. Thus, compound 5: may be a promising candidate for the treatment of cancer or inflammatory diseases related to the IL-6/STAT3 signaling pathway.

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Inhibition of STAT3 phosphorylation by sulforaphane reduces adhesion molecule expression in vascular endothelial cell

Cited by 16 publications

References 21 publications

FGFR2/STAT3 Signaling Pathway Involves in the Development of MMTV-Related Spontaneous Breast Cancer in TA2 Mice

FGFR2/STAT3 Signaling Pathway Involves in the Development of MMTV-Related Spontaneous Breast Cancer in TA2 Mice

Chrysin Attenuates VCAM-1 Expression and Monocyte Adhesion in Lipopolysaccharide-Stimulated Brain Endothelial Cells by Preventing NF-κB Signaling

Diarylheptanoids from Curcuma phaeocaulis Suppress IL-6-Induced STAT3 Activation

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