STAT3 transcription factor as target for anti-cancer therapy

Mohassab, Aliaa M.; Hassan, Heba A.; Abdelhamid, Dalia; Abdel‐Aziz, Mohamed

doi:10.1007/s43440-020-00156-5

Cited by 44 publications

(38 citation statements)

References 226 publications

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“…Since STAT3 serves vital roles in the progression of most human cancer types, it has been suggested that STAT3 could be an important candidate therapeutic target for tumor treatment (34). It has also been reported that different mechanisms are involved in STAT3 inhibition, including suppression of tyrosine enzymes that contribute to the phosphorylation or activation of STAT3, inhibition of STAT3-mediated transcription, repression of nuclear localization of STAT3 and inhibition of the interaction between STAT3 and its target gene (35). Nevertheless, remains unknown if and how chidamide influences STAT3 in DLBCL cells.…”

Section: Discussionmentioning

confidence: 99%

Chidamide induces apoptosis in DLBCL cells by suppressing the HDACs/STAT3/Bcl‑2 pathway

et al. 2021

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Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous malignant tumor type, and epigenetic modifications such as acetylation or deacetylation serve vital roles in its development. Chidamide, a novel histone deacetylase inhibitor, exerts an anticancer effect against various types of cancer. The present study aimed to evaluate the cellular effect of chidamide on a number of DLBCL cell lines and to investigate its underlying mechanism. The results demonstrated that chidamide induced the death of these cells in a concentration-(0-30 µmol/l) and time-dependent (24-72 h) manner, as determined using the Cell Counting Kit-8 cell viability assay. Moreover, chidamide promoted cellular apoptosis, which was identified via flow cytometry and western blot analysis, with an increase in cleaved caspase-3 expression and a decrease in Bcl-2 expression. Chidamide treatment also decreased the expression level of STAT3 and its phosphorylation, which was accompanied by the downregulation of a class-I histone deacetylase (HDAC) inhibitor, chidamide. Collectively, these data suggested that chidamide can be a potent therapeutic agent to treat DLBCL by inducing the apoptotic death of DLBCL cells by inhibiting the HDACs/STAT3/Bcl-2 pathway.

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Section: Discussionmentioning

confidence: 99%

Chidamide induces apoptosis in DLBCL cells by suppressing the HDACs/STAT3/Bcl‑2 pathway

et al. 2021

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“…Activated nuclear STAT3 has been detected in multiple forms of leukaemia [ 193 , 197 , 208 , 209 , 210 , 211 ]. The STAT 3 activation has also shown to contribute to multidrug resistance (MDR).…”

Section: Molecular Mechanisms Of Polyphenolsmentioning

confidence: 99%

“…The elevation in the activity of STAT 3 enhances leukaemia cells such as AML and CML to be resistant to tyrosine kinase inhibitors (TKI) [ 212 , 213 ]. There are different suggested strategies for STAT3 inhibition, including: firstly, the inhibition of multiple tyrosine kinase pathways of many growth factor receptors such as JAKs, EGFR, and intracellular SFKs which are responsible for the activation/phosphorylation of STAT3 [ 208 ]. Secondly, inhibition of protein–protein interactions that involved in STAT3 signalling [ 208 ].…”

Section: Molecular Mechanisms Of Polyphenolsmentioning

confidence: 99%

“…There are different suggested strategies for STAT3 inhibition, including: firstly, the inhibition of multiple tyrosine kinase pathways of many growth factor receptors such as JAKs, EGFR, and intracellular SFKs which are responsible for the activation/phosphorylation of STAT3 [ 208 ]. Secondly, inhibition of protein–protein interactions that involved in STAT3 signalling [ 208 ]. Furthermore, inhibition of STAT3-mediated transcription [ 208 ].…”

Section: Molecular Mechanisms Of Polyphenolsmentioning

confidence: 99%

“…Secondly, inhibition of protein–protein interactions that involved in STAT3 signalling [ 208 ]. Furthermore, inhibition of STAT3-mediated transcription [ 208 ]. Finally, inhibition of nuclear import and export (translocation) of STAT3 [ 208 ].…”

Section: Molecular Mechanisms Of Polyphenolsmentioning

confidence: 99%

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Molecular Action of Polyphenols in Leukaemia and Their Therapeutic Potential

Alaswad

Mahbub

Maitre

et al. 2021

IJMS

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Leukaemia is a malignant disease of the blood. Current treatments for leukaemia are associated with serious side-effects. Plant-derived polyphenols have been identified as potent anti-cancer agents and have been shown to work synergistically with standard chemotherapy agents in leukaemia cell lines. Polyphenols have multiple mechanisms of action and have been reported to decrease cell proliferation, arrest cell cycle and induce apoptosis via the activation of caspase (3, 8 and 9); the loss of mitochondrial membrane potential and the release of cytochrome c. Polyphenols have been shown to suppress activation of transcription factors, including NF-kB and STAT3. Furthermore, polyphenols have pro-oxidant properties, with increasing evidence that polyphenols inhibit the antioxidant activity of glutathione, causing oxidative DNA damage. Polyphenols also induce autophagy-driven cancer cell death and regulate multidrug resistance proteins, and thus may be able to reverse resistance to chemotherapy agents. This review examines the molecular mechanism of action of polyphenols and discusses their potential therapeutic targets. Here, we discuss the pharmacological properties of polyphenols, including their anti-inflammatory, antioxidant, anti-proliferative, and anti-tumour activities, and suggest that polyphenols are potent natural agents that can be useful therapeutically; and discuss why data on bioavailability, toxicity and metabolism are essential to evaluate their clinical use.

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ETV4 transcriptionally activates HES1 and promotes Stat3 phosphorylation to promote malignant behaviors of colon adenocarcinoma

Yao

Bao²,

et al. 2021

Cell Biology International

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Colon adenocarcinoma (COAD) is the commonest type of colorectal cancer with high morbidity and mortality worldwide. ETS variant 4 (ETV4) is a member of the ETS transcription factors and is frequently involved in the progression of many cancers. This study focused on the relevance of ETV4 to the progression of COAD. ETV4 was highly expressed in the collected COAD tissues and acquired cells and indicated advanced Dukes staging in patients. Knockdown of ETV4 in COAD cells weakened proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) activity of cells. The downstream genes of ETV4 were predicted, and a Gene Ontology (GO) analysis was conducted to identify the key molecule involved. ETV4 bound to the promoter sequence of HES1 and activated its transcription. Further overexpression of HES1 restored the malignant behaviors of COAD cells. HES1 was also found to promote phosphorylation of Stat3. Similar results were reproduced in vivo where downregulation of ETV4 blocked the growth of xenograft tumors in nude mice. This study demonstrated that ETV4 encourages malignant development of COAD through activating HES1 transcription and Stat3 phosphorylation. This study may offer novel insights into COAD therapy.

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STAT3 transcription factor as target for anti-cancer therapy

Cited by 44 publications

References 226 publications

Chidamide induces apoptosis in DLBCL cells by suppressing the HDACs/STAT3/Bcl‑2 pathway

Chidamide induces apoptosis in DLBCL cells by suppressing the HDACs/STAT3/Bcl‑2 pathway

Molecular Action of Polyphenols in Leukaemia and Their Therapeutic Potential

ETV4 transcriptionally activates HES1 and promotes Stat3 phosphorylation to promote malignant behaviors of colon adenocarcinoma

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