EGFR-mediated apoptosis via STAT3

Jackson, Nicole M.; Ceresa, Brian P.

doi:10.1016/j.yexcr.2017.04.016

Cited by 39 publications

(34 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In order to assess whether the chemosensitizing effects of β-caryophyllene (50 µM) towards doxorubicin were dependent on STAT3, we also tested the substances and their combination in human prostatic PC3 cells ( Figure S4), known to be lacking in the expression of STAT3 [66,67]. Under our experimental conditions, the cytotoxic effect of doxorubicin was slightly increased by β-caryophyllene, although no statistical difference was found in the IC 50 values (48.4, C.L.…”

Section: Effect Of β-Caryophyllene In Combination With Doxorubicin Onmentioning

confidence: 99%

Modulation of STAT3 Signaling, Cell Redox Defenses and Cell Cycle Checkpoints by β-Caryophyllene in Cholangiocarcinoma Cells: Possible Mechanisms Accounting for Doxorubicin Chemosensitization and Chemoprevention

Sotto

Giacomo

Rubini

et al. 2020

Cells

View full text Add to dashboard Cite

Cholangiocarcinoma (CCA) is an aggressive group of biliary tract cancers, characterized by late diagnosis, low effective chemotherapies, multidrug resistance, and poor outcomes. In the attempt to identify new therapeutic strategies for CCA, we studied the antiproliferative activity of a combination between doxorubicin and the natural sesquiterpene β-caryophyllene in cholangiocarcinoma Mz-ChA-1 cells and nonmalignant H69 cholangiocytes, under both long-term and metronomic schedules. The modulation of STAT3 signaling, oxidative stress, DNA damage response, cell cycle progression and apoptosis was investigated as possible mechanisms of action. β-caryophyllene was able to synergize the cytotoxicity of low dose doxorubicin in Mz-ChA-1 cells, while producing cytoprotective effects in H69 cholangiocytes, mainly after a long-term exposure of 24 h. The mechanistic analysis highlighted that the sesquiterpene induced a cell cycle arrest in G2/M phase along with the doxorubicin-induced accumulation in S phase, reduced the γH2AX and GSH levels without affecting GSSG. ROS amount was partly lowered by the combination in Mz-ChA-1 cells, while increased in H69 cells. A lowered expression of doxorubicin-induced STAT3 activation was found in the presence of β-caryophyllene in both cancer and normal cholangiocytes. These networking effects resulted in an increased apoptosis rate in Mz-ChA-1 cells, despite a lowering in H69 cholangiocytes. This evidence highlighted a possible role of STAT3 as a final effector of a complex network regulated by β-caryophyllene, which leads to an enhanced doxorubicin-sensitivity of cholangiocarcinoma cells and a lowered chemotherapy toxicity in nonmalignant cholangiocytes, thus strengthening the interest for this natural sesquiterpene as a dual-acting chemosensitizing and chemopreventive agent.

show abstract

Section: Effect Of β-Caryophyllene In Combination With Doxorubicin Onmentioning

confidence: 99%

Modulation of STAT3 Signaling, Cell Redox Defenses and Cell Cycle Checkpoints by β-Caryophyllene in Cholangiocarcinoma Cells: Possible Mechanisms Accounting for Doxorubicin Chemosensitization and Chemoprevention

Sotto

Giacomo

Rubini

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…However, when overexpressed, STAT3 promoted apoptosis through induction of the expression of caspase-3 [169]. Furthermore, mitoSTAT3 contribute to anti-apoptotic functions in tumour cells by increasing the MMP and inhibiting the opening of the MPTP to release Ca 2+ and cytochrome c into cytosol which would lead to intrinsic apoptosis as demonstrated in human esophageal squamous cell carcinoma (ESCC) [170,171]. Therefore, the role of STAT3 in apoptosis depends not only on the localization of STAT3, but its levels.…”

Section: Stat3 As a Regulatory Buffer Of Apoptosis And Autophagymentioning

confidence: 99%

A STAT3 of Addiction: Adipose Tissue, Adipocytokine Signalling and STAT3 as Mediators of Metabolic Remodelling in the Tumour Microenvironment

Kadye

Stoffels

Fanucci

et al. 2020

Cells

View full text Add to dashboard Cite

Metabolic remodelling of the tumour microenvironment is a major mechanism by which cancer cells survive and resist treatment. The pro-oncogenic inflammatory cascade released by adipose tissue promotes oncogenic transformation, proliferation, angiogenesis, metastasis and evasion of apoptosis. STAT3 has emerged as an important mediator of metabolic remodelling. As a downstream effector of adipocytokines and cytokines, its canonical and non-canonical activities affect mitochondrial functioning and cancer metabolism. In this review, we examine the central role played by the crosstalk between the transcriptional and mitochondrial roles of STAT3 to promote survival and further oncogenesis within the tumour microenvironment with a particular focus on adipose-breast cancer interactions.

show abstract

“…Apoptosis is also part of the regular turnover of the SG, when exhausted saliva-producing acinar cells die, and are replaced with new cells generated from progenitor cells. Enhanced EGF signaling, critical to epithelial cell and SGPC homeostasis, and also involved with STAT3-based cytokine signaling, can also result in apoptosis [93]. This provides an additional explanation for enhanced apoptotic levels observed in the epithelium of pSS patients, and also further confirms the complicity of STAT3 in a multitude of salient pathways.…”

Section: Inhibitors Of Apoptosismentioning

confidence: 57%

Small-molecule inhibitors and the salivary gland epithelium in Sjögren’s syndrome

Pringle

Wang

Bootsma

et al. 2019

Expert Opinion on Investigational Drugs

View full text Add to dashboard Cite

Introduction: The salivary gland (SG) in primary Sjögren's syndrome (pSS) is characterized by its lack of function (hyposalivation) and lymphocytic invasion. Small-molecule inhibitors (SMIs) are a new class of drugs, whose diminutive size permits diffusion into cells. SMIs targeting components of the immune system are eagerly being trialed for their potential therapeutic utility in pSS. Neglected until now, however, is a discussion of the potential effects of SMIs on the SG epithelium. Areas covered: We begin by reminding the reader of the SG epithelial compartment, its complicity in inflammatory milieu formation in pSS, and categories of SMIs which merit attention. We discuss each SMI category, including pre-clinical data concerning pSS and likely consequences of their application on the SG epithelium. Expert opinion: Recovery of saliva production in pSS requires restoring the function of the SG epithelium, not solely on inflammation resolution. Many SMIs, for example, those blocking JAK-STAT signaling, interfere with critical epithelial cell pathways, most notably EGF signaling. If the effect of SMIs on SG epithelium is ignored, recovery of SG function will be challenging. We predict that NFκB signaling blockade will impart the least SG epithelium damage whilst reducing inflammation and facilitating recovery from hyposalivation in pSS.

show abstract

EGFR-mediated apoptosis via STAT3

Cited by 39 publications

References 83 publications

Modulation of STAT3 Signaling, Cell Redox Defenses and Cell Cycle Checkpoints by β-Caryophyllene in Cholangiocarcinoma Cells: Possible Mechanisms Accounting for Doxorubicin Chemosensitization and Chemoprevention

Modulation of STAT3 Signaling, Cell Redox Defenses and Cell Cycle Checkpoints by β-Caryophyllene in Cholangiocarcinoma Cells: Possible Mechanisms Accounting for Doxorubicin Chemosensitization and Chemoprevention

A STAT3 of Addiction: Adipose Tissue, Adipocytokine Signalling and STAT3 as Mediators of Metabolic Remodelling in the Tumour Microenvironment

Small-molecule inhibitors and the salivary gland epithelium in Sjögren’s syndrome

Contact Info

Product

Resources

About