Quercetin inhibits epithelial&amp;ndash;mesenchymal transition, decreases invasiveness and metastasis, and reverses IL-6 induced epithelial&amp;ndash;mesenchymal transition, expression of MMP by inhibiting STAT3 signaling in pancreatic cancer cells

Yu, Dinglai; Ye, Tingting; Xiang, Yukai; Shi, Zhehao; Zhang, Jie; Liu, Bin; Zhang, Fan; Chen, Bicheng; Zhou, Mengtao

doi:10.2147/ott.s136840

Cited by 85 publications

(67 citation statements)

References 44 publications

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“…20 It is also testified that the effect of QE is against F I G U R E 6 The underlying mechanism of the antitumor effect of QE the biological activity of migration and invasion by inhibiting STAT3. 16,18 At the same time, our results showed that QE could remit the changes brought by IL-6.Thus, we confirmed that QE could reverse the changes caused by STAT3 activation ( Figure 6). In accordance with expectations, we came to a conclusion, that is, the antitumor effect of QE was at least depending on its abrogation of the JAK2/STAT3 pathway.…”

Section: Discussionsupporting

confidence: 77%

“…Our previous studies have shown that quercetin could protect the liver from concanavalin A‐induced acute hepatitis, ischemia reperfusion injury, and fibrosis . Others have reported that quercetin had effective anticancer functions in hepatocellular carcinoma and this function may have a close relationship with the STAT3 pathway . As a cytokine, the transcription factor STAT3, has been testified that it is closely associated with tumor development.…”

Section: Introductionmentioning

confidence: 99%

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Quercetin shows anti‐tumor effect in hepatocellular carcinoma LM3 cells by abrogating JAK2/STAT3 signaling pathway

Liu

et al. 2019

Cancer Medicine

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140

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Objective Hepatocellular carcinima is one of the most common tumors in clinic and also one of the leading causes of death from cancer worldwide. Quercetin shows significant effects on blocking the development of various cancers. Methods We used the human hepatocellular carcinoma LM3 and nude mice tumor model to assess the effects of quercetin in hepatocellular carcinoma and clarify its mechanism of action. We collected LM3 cell line treated with different doses of quercetin at different time periods and determined the vital indexes. The liver tissues of mice were collected and used for western boltting (WB), Hematoxylin and Eosin (H&E) and TUNEL staining. Results Results indicated that quercetin suppressed the Hepatocellular carcinoma (HCC) growth both in vivo and in vitro. Quercetin could disturb LM3 cells proliferation and cell cycle distribution, thus inducing apoptosis. At the same time, quercetin inhibited LM3 cells migration and invasion and promoted HCC autophagy. These effects at least partly depended on the down‐regulation of the activation of JAK2 and STAT3 by quercetin. Conclusion Quercetin inhibited hepatocellular carcinoma progression by modulating cell apoptosis, migration, invasion, and autophagy; and its effects were at least partly related with the JAK2/STAT3 signaling pathway.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Quercetin shows anti‐tumor effect in hepatocellular carcinoma LM3 cells by abrogating JAK2/STAT3 signaling pathway

Liu

et al. 2019

Cancer Medicine

Self Cite

140

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“…The other compound, quercetin, is a flavonoid widely distributed in fruits, vegetables, and beverages that shows antioxidative, anti inflammatory, and anticancer properties. Quercetin reversed IL‐6‐induced EMT in pancreatic cancer cells through STAT3 . Collectively, the data indicate that the use of compounds targeting STAT3 might be an effective approach for curing fibrosis and cancer.…”

Section: Small Molecules Against Emtmentioning

confidence: 99%

“…Quercetin reversed IL-6-induced EMT in pancreatic cancer cells through STAT3. 44 Collectively, the data indicate that the use of compounds targeting STAT3 might be an effective approach for curing fibrosis and cancer.…”

mentioning

confidence: 99%

Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

Feng

Chen

Vaziri

et al. 2019

Medicinal Research Reviews

109

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Tissue fibrosis and cancer both lead to high morbidity and mortality worldwide; thus, effective therapeutic strategies are urgently needed. Because drug resistance has been widely reported in fibrotic tissue and cancer, developing a strategy to discover novel targets for targeted drug intervention is necessary for the effective treatment of fibrosis and cancer. Although many factors lead to fibrosis and cancer, pathophysiological analysis has demonstrated that tissue fibrosis and cancer share a common process of epithelial‐mesenchymal transition (EMT). EMT is associated with many mediators, including transcription factors (Snail, zinc‐finger E‐box‐binding protein and signal transducer and activator of transcription 3), signaling pathways (transforming growth factor‐β1, RAC‐α serine/threonine‐protein kinase, Wnt, nuclear factor‐kappa B, peroxisome proliferator‐activated receptor, Notch, and RAS), RNA‐binding proteins (ESRP1 and ESRP2) and microRNAs. Therefore, drugs targeting EMT may be a promising therapy against both fibrosis and tumors. A large number of compounds that are synthesized or derived from natural products and their derivatives suppress the EMT by targeting these mediators in fibrosis and cancer. By targeting EMT, these compounds exhibited anticancer effects in multiple cancer types, and some of them also showed antifibrotic effects. Therefore, drugs targeting EMT not only have both antifibrotic and anticancer effects but also exert effective therapeutic effects on multiorgan fibrosis and cancer, which provides effective therapy against fibrosis and cancer. Taken together, the results highlighted in this review provide new concepts for discovering new antifibrotic and antitumor drugs.

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“…6 More important, quercetin inhibited EMT along with reduction in the secretion of MMPs. 6 More important, quercetin inhibited EMT along with reduction in the secretion of MMPs.…”

Section: Jak-stat3mentioning

confidence: 99%

Quercetin‐mediated regulation of signal transduction cascades and microRNAs: Natural weapon against cancer

Farooqı

Jabeen

Attar

et al. 2018

J of Cellular Biochemistry

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Recent technological and analytical breakthroughs in genomics and proteomics have deepened our understanding related to the multifaceted nature of cancer. Because of therapeutically challenging nature of cancer, there has been a renewed interest in phytochemistry, and much attention is currently being given to the identification of signaling pathway inhibitors. Data obtained through high-throughput technologies has provided a broader landscape of wiring maps of complex oncogenic signaling networks, thus revealing novel therapeutic opportunities. Increasingly, it is being realized that although our knowledge related to physiological and pathophysiological roles of signal transduction cascades has evolved rapidly, the clinical development of signaling pathway inhibitors has been challenging. Quercetin has attracted considerable attention because of its amazingly high pharmacological value. Research over decades has sequentially shown that quercetin effectively inhibited cancer development and progression. In this review, we have attempted to set the spotlight on the regulation of different cell signaling pathways by quercetin. We partition this multicomponent review into how quercetin effectively regulates the Wnt/β-catenin pathway, Janus kinase-signal transducer and activator of transcription pathway, and vascular endothelial growth factor/vascular endothelial growth factor receptor signaling cascade in different types of cancers. We also provide an overview of the regulation of NOTCH and SHH pathways by quercetin. MicroRNAs (miRNAs) have also emerged as versatile regulators of cancer, and contemporary studies have shed light on the ability of quercetin to control different miRNAs in various cancers. We have scattered information related to NOTCH and SHH pathways, and future studies must converge on the investigation of these pathways to see how quercetin modulates the signaling machinery of these pathways.

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Quercetin inhibits epithelial–mesenchymal transition, decreases invasiveness and metastasis, and reverses IL-6 induced epithelial–mesenchymal transition, expression of MMP by inhibiting STAT3 signaling in pancreatic cancer cells

Cited by 85 publications

References 44 publications

Quercetin shows anti‐tumor effect in hepatocellular carcinoma LM3 cells by abrogating JAK2/STAT3 signaling pathway

Quercetin shows anti‐tumor effect in hepatocellular carcinoma LM3 cells by abrogating JAK2/STAT3 signaling pathway

Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

Quercetin‐mediated regulation of signal transduction cascades and microRNAs: Natural weapon against cancer

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