In vitro studies confirmed this notion and found that CRP was able to upregulate both CD32 and CD64 and induced FLS proliferation, invasion, and pro inflammatory expression by increasing production of CCL2, CXCL8, IL-6, MMP2, MMP9 while suppressing an anti-inflammatory cytokine IL-10 expression.

In vitro studies confirmed this notion and found that CRP was able to upregulate both CD32 and CD64 and induced FLS proliferation, invasion, and pro inflammatory expression by increasing production of CCL2, CXCL8, IL-6, MMP2, MMP9 while suppressing an anti-inflammatory cytokine IL-10 expression.

As shown in XREF_FIG, multiplex cytokine assay kits assays showed that addition of CRP dose-dependently upregulated CCL2, CXCL8, IL-6, MMP2, MMP9 in RA-FLS but not in HFLS, although expression of IL-1beta and TNFalpha was not significantly changed (XREF_FIG).

In vitro studies confirmed this notion and found that CRP was able to upregulate both CD32 and CD64 and induced FLS proliferation, invasion, and pro inflammatory expression by increasing production of CCL2, CXCL8, IL-6, MMP2, MMP9 while suppressing an anti-inflammatory cytokine IL-10 expression.

As shown in XREF_FIG, multiplex cytokine assay kits assays showed that addition of CRP dose-dependently upregulated CCL2, CXCL8, IL-6, MMP2, MMP9 in RA-FLS but not in HFLS, although expression of IL-1beta and TNFalpha was not significantly changed (XREF_FIG).

In vitro studies confirmed this notion and found that CRP was able to upregulate both CD32 and CD64 and induced FLS proliferation, invasion, and pro inflammatory expression by increasing production of CCL2, CXCL8, IL-6, MMP2, MMP9 while suppressing an anti-inflammatory cytokine IL-10 expression.

As shown in XREF_FIG, multiplex cytokine assay kits assays showed that addition of CRP dose-dependently upregulated CCL2, CXCL8, IL-6, MMP2, MMP9 in RA-FLS but not in HFLS, although expression of IL-1beta and TNFalpha was not significantly changed (XREF_FIG).

In vitro studies confirmed this notion and found that CRP was able to upregulate both CD32 and CD64 and induced FLS proliferation, invasion, and pro inflammatory expression by increasing production of CCL2, CXCL8, IL-6, MMP2, MMP9 while suppressing an anti-inflammatory cytokine IL-10 expression.

As shown in XREF_FIG, multiplex cytokine assay kits assays showed that addition of CRP dose-dependently upregulated CCL2, CXCL8, IL-6, MMP2, MMP9 in RA-FLS but not in HFLS, although expression of IL-1beta and TNFalpha was not significantly changed (XREF_FIG).

In vitro studies confirmed this notion and found that CRP was able to upregulate both CD32 and CD64 and induced FLS proliferation, invasion, and pro inflammatory expression by increasing production of CCL2, CXCL8, IL-6, MMP2, MMP9 while suppressing an anti-inflammatory cytokine IL-10 expression.

This was further confirmed by the ability of pre-treating RA-FLS with a NF-kappaB inhibitor, PDTC (100 mumol/L) to inhibit CRP induced proliferation (XREF_FIG) and upregulation of CXCL8, CCL2.

CRP can induce synovial inflammation via mechanisms associated with activation of CD32/64-p 38 and NF-kappaB signaling.

Here we tested the hypothesis that CRP may be produced locally by FLSs and functions to induce the synovial inflammation in patients with RA.

CRP may promote synovial inflammation via mechanism associated with activation of CD32/64- p38 and NF-kappaB signaling.

In the present study, we found that CRP signaled primarily through CD32, to a less extent of CD64, to differentially regulate joint inflammation.

CRP Promotes RA-FLS Pro inflammatory Response Differentially via the CD32/64-p 38 and NF-kappaB-Dependent Mechanisms in vitro.

This was supported by the findings that CRP induced activation of p38 MAP kinase and NF-kappaB signaling was blunted by neutralizing antibodies against CD32 but not CD64.

To examine whether CRP induces NF-kappaB nuclear translation, immunofluorescence and subcellular fractionation were performed.

S100A8 Induced Pro Inflammatory Cytokine Production Via Phosphorylation of ERK and JNK in BV-2 Cells.

Also, the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular-signal-regulated kinase (ERK) were stimulated by S100A8, which had an analogous effect to the lipopolysaccharide (LPS) treatment (XREF_FIG C-E).

S100A8 Induced Pro Inflammatory Cytokine Production Via Phosphorylation of ERK and JNK in BV-2 Cells.

Also, the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular-signal-regulated kinase (ERK) were stimulated by S100A8, which had an analogous effect to the lipopolysaccharide (LPS) treatment (XREF_FIG C-E).

The S100A8 knockdown using shRNA revealed that COX-2 and PGE 2 expression was regulated by S100A8, which suggested that the intracellular increase of microglial S100A8 levels upregulated COX-2 expression and PGE2 secretion, contributing to neuronal death under hypoxic conditions.

In agreement with previous reports, the results of this study confirmed that S100A8 significantly increased the production of IL-6, TNF-alpha, and IL-1beta.

In agreement with previous reports, the results of this study confirmed that S100A8 significantly increased the production of IL-6, TNF-alpha, and IL-1beta.

These results strongly suggested that S100A8 induced the NLRP3 inflammasome priming via NF-kappaB activation.

The results suggested that S100A8, secreted by neuronal cells under hypoxic conditions, triggered the priming of NLRP3 in microglial cells, through the TLR4 and NF-kappaB signaling.

In addition, the translocation of NF-kB, which played a pivotal role in regulating the expression and activation of NLRP3, was also increased when cells were treated with S100A8.

These results suggested that S100A8, secreted by neuronal cells under hypoxic conditions, combined with TLR4 of microglia cells, activated the NLRP3 inflammasome priming.

In agreement with previous reports, the results of this study confirmed that S100A8 significantly increased the production of IL-6, TNF-alpha, and IL-1beta.

However, for the first time, we showed that up-regulation of microglial S100A8 levels increased neuronal apoptosis after hypoxia, in primary multicellular cultures consisting of neurons, astrocytes, and microglia.

Therefore, this study determined whether S100A8 induced neuronal apoptosis during cerebral hypoxia and elucidated its mechanism of action using in vitro systems, including astrocytes and microglial and neuronal cells, under hypoxic conditions.

S100A8 Knockdown on Microglia Attenuated Neuronal Apoptosis by Hypoxia.

To investigate whether S100A8 expression in microglia induced apoptosis of neuronal cells under hypoxic condition, SH-SY5Y cells were co-cultured with BV-2 cells transfected with S100A8 shRNA for 48 h in a 0.4 mum pore transwell system and under hypoxic conditions (XREF_FIG A, B).

These findings indicated that the expression of S100A8, induced in microglia cells under hypoxic conditions, activated COX-2 expression and PGE 2 secretion to induce the apoptosis of neurons.

FACS analysis showed that the increase of S100A8 levels in microglia by hypoxia promoted neuronal apoptosis, which was confirmed by immunofluorescence.

Knockdown of S100A8 levels by using shRNA revealed that microglial S100A8 expression activated COX-2 expression, leading to neuronal apoptosis under hypoxia.

S100A8, secreted from neurons under hypoxia, activated the secretion of tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6) through phosphorylation of extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) in microglia.

S100A8, secreted from neurons under hypoxia, activated the secretion of tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6) through phosphorylation of extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) in microglia.

The aim of this study was to determine whether S100A8 induced neuronal apoptosis during cerebral hypoxia and elucidate its mechanism of action.

The coherent molecular mechanisms underlying the NO related inhibition of IDO remain unknown.

The antioxidant properties of IDO were proven, so the inhibiting of IDO by NO may restrict the antioxidant properties and induce increased free radicals.

In vivo studies indicate that NO can inhibit IDO catalytic activity by directly interacting [XREF_BIBR] or by stimulating IDO degradation through the proteasome pathway [XREF_BIBR].

Cells expressing IDO can co-express iNOS in response to IFN-gamma, which produces NO that inhibits, in turn, IDO.

Previous studies have suggested nitric oxide (NO) can inhibit IDO activity and expression [XREF_BIBR, XREF_BIBR] most likely through post-translational regulation leading to proteasomal degradation of IDO rather than transcriptional regulation [XREF_BIBR].

Previous studies have suggested nitric oxide (NO) can inhibit IDO activity and expression [XREF_BIBR, XREF_BIBR] most likely through post-translational regulation leading to proteasomal degradation of IDO rather than transcriptional regulation [XREF_BIBR].

For example, nitric oxide (NO) production may block IDO enzyme activity since NO inhibits the activity of heme containing enzymes such as IDO (Thomas et al., 2001).

For example, nitric oxide (NO) production may block IDO enzyme activity since NO inhibits the activity of heme containing enzymes such as IDO (Thomas et al., 2001).

In sharp contrast to macrophages, murine microglial cell clones immortalized with the activated c-myc oncogene have been reported to be resistant to NO inhibition of IDO.

In conclusion, results of the present series of experiments indicate that IDO in primary murine microglia costimulated with IFNgamma + LPS is not impaired by the production of NO, as is known to occur in murine macrophages.

Conversely, induction of NO by activation of iNOS down-regulates IDO activity in cell types as diverse as human uroepithelial transformed cells, murine bone marrow derived myeloid dendritic cells, human transformed and primary macrophages and mouse peritoneal cells.

As a result of this crosstalk, NO is well known to inhibit IDO activity in many types of cells.

In addition, direct binding of NO to heme iron in IDO, which is one of the mechanisms by which NO inhibits IDO at the post-translational level, is dependent on a number of cellular factors, including NO abundance, pH, redox environment and tryptophan availability.

NO inhibition of IDO is apparently specific to both certain species and cell types.

In macrophages, the inhibition of IDO by NO occurs at both the transcriptional and post-transcriptional levels.

Previous studies have reported that NO is able to inhibit the activity of IDO by reacting with the heme iron situated in its active site.

NO inhibits IDO at the transcriptional level and accelerates the decomposition of IDO protein, thereby affecting its stability.

Therefore, simultaneous induction of nitric oxide, respiratory burst and tryptophan degradation responses would antagonize PKC and thus NADPH oxidase activation and the IDO enzyme.

Several findings have demonstrated that NO is able to inhibit the IDO enzyme by direct interaction or accelerating proteasomal degradation [XREF_BIBR, XREF_BIBR].

Although not yet examined in the context of exercise, nitric oxide has been shown to inhibit IDO activity.

33 Thus, a strong rationale suggests that exercise induced changes in nitric oxide may mediate an inhibition of IDO activity, possibly leading to a chronic downregulation and stabilization of the KYN pathway as reported by Zimmer et al. 23 The mechanisms underlying both acute and chronic exercise induced elevations in the metabolic flux towards KA could be driven by KAT expression in different tissues or cell types.

XREF_BIBR Nitric oxide, interleukin-4, peroxynitrite and transforming growth factor beta inhibit IDO-1 but it is unclear whether these also inhibit IDO-2.

XREF_BIBR 3-HAA also inhibits nitric oxide synthetase (although not in microglial cells) and nuclear factor kappaB expression; XREF_BIBR, XREF_BIBR of which the former could result in positive feedback and upregulation of IDO activity, which is inhibited by nitric oxide, as well as neuronal dysfunction through impairment of nitric oxide 's neurotransmitter function.

Furthermore, CCL11 induced the mRNA expression of CCL11 and CCR3.

Furthermore, CCL11 induced the mRNA expression of CCL11 and CCR3.

The results of the present study demonstrated that FBXW7 efficiently inhibited SKOV3 cell invasion and migration, as well as tube formation of HUVECs.

It has also been reported that FBXW7 suppresses oral squamous cell carcinoma proliferation and invasion regulated by miR-27a through the PI3K and AKT signaling pathway.

The results of the present study demonstrated that overexpression of FBXW7 inhibited the invasion, migration, EMT and angiogenesis of OC cells.

In conclusion, the results of the present study demonstrated that FBXW7 inhibited the invasion, migration and angiogenesis of OC cells.

Previous studies have demonstrated that beta-catenin signaling helps VEGF regulate angiogenesis, and that FBXW7 promotes the degradation of beta-catenin.

It has also been reported that FBXW7 suppresses oral squamous cell carcinoma proliferation and invasion regulated by miR-27a through the PI3K and AKT signaling pathway.

The results of the present study demonstrated that overexpression of FBXW7 inhibited the invasion, migration, EMT and angiogenesis of OC cells.

The results of the present study demonstrated that overexpression of FBXW7 inhibited the invasion, migration, EMT and angiogenesis of OC cells.

In conclusion, the results of the present study demonstrated that FBXW7 inhibited the invasion, migration and angiogenesis of OC cells.

Notably, overexpression of FBXW7 significantly decreased VEGF mRNA and protein expression compared with the vector control group (XREF_FIG and XREF_FIG).

Collectively, these results indicated that overexpression of FBXW7 inhibited the invasion, migration and EMT process of OC cells by suppressing VEGF expression.

Overall, these results suggested that overexpression of FBXW7 suppressed the angiogenesis of OC cells by suppressing VEGF expression.

The present study aimed to investigate VEGF expression following overexpression of FBXW7 in OC cells.

FBXW7 inhibits invasion, migration and angiogenesis in ovarian cancer cells by suppressing VEGF expression through inactivation of beta-catenin signaling.

Subsequently, FBXW7 was overexpressed to determine VEGF expression in SKOV3 cells.

Overall, the results of the present study suggested that FBXW7 inhibited invasion, migration and angiogenesis of OC cells by suppressing VEGF expression through inactivation of beta-catenin signaling.

Furthermore, overexpression of FBXW7 markedly suppressed beta-catenin and c-Myc expression, whereas the decreased expression levels of VEGF, VEGFR1 and VEGFR2 following overexpression of FBXW7 were increased after treatment of SKOV3 cells with LiCl.

As presented in XREF_FIG, overexpression of FBXW7 significantly decreased the expression levels of beta-catenin and c-Myc compared with the empty vector group.

The results of the present study demonstrated that overexpression of FBXW7 inhibited the expression levels of VEGF, beta-catenin and c-Myc.

As presented in XREF_FIG, overexpression of FBXW7 significantly decreased the expression levels of beta-catenin and c-Myc compared with the empty vector group.

The results of the present study demonstrated that overexpression of FBXW7 inhibited the expression levels of VEGF, beta-catenin and c-Myc.

Furthermore, overexpression of FBXW7 markedly suppressed beta-catenin and c-Myc expression, whereas the decreased expression levels of VEGF, VEGFR1 and VEGFR2 following overexpression of FBXW7 were increased after treatment of SKOV3 cells with LiCl.

FBXW7 inhibits VEGF expression through inactivation of beta-catenin signaling.

Collectively, these results suggested that FBXW7 may inhibit VEGF expression through inactivation of beta-catenin signaling in SKOV3 cells.

Mechanistically, FBXW7 suppressed VEGF expression by inactivating beta-catenin signaling.

The results of the present study demonstrated that overexpression of FBXW7 suppressed VEGF expression, while overexpression of VEGF partially counteracted the inhibitory effects of FBXW7 overexpression on the invasion, migration, EMT and angiogenesis of OC cells.

Overall, the current results suggested that FBXW7 may inhibit VEGF expression through inactivation of beta-catenin signaling in SKOV3 cells.

The results of the present study demonstrated that overexpression of FBXW7 inhibited the expression levels of VEGF, beta-catenin and c-Myc.

Overexpression of FBXW7 significantly downregulates VEGF expression in OC cells.

Overall, these results suggested that overexpression of FBXW7 inhibited VEGF expression in OC cells.

Overexpression of FBXW7 significantly decreased VEGF expression in SKOV3 cells.

The results demonstrated that overexpression of FBXW7 downregulated the expression levels of CD31, VEGFR1 and VEGFR, whereas co-transfection with FBXW7 and VEGF plasmids significantly increased their expression levels compared with the Ov-FBXW7+ pc-NC group (XREF_FIG and XREF_FIG), which is consistent with the results of the tube formation assay.

For instance, FBXW7 can target salt inducible kinase 2 for degradation, leading to the disruption of target of rapamycin 2-AKT signaling to inhibit pancreatic cancer cell proliferation and cell cycle progression.

Limonin induces apoptosis of HL-60 cells by inhibiting NQO1 activity.

Limonin induces apoptosis of HL-60 cells by inhibiting NQO1 activity.

At the same time, limonin down-regulated the expression of NQO1, indicating that limonin may indirectly act on the apoptosis pathway by regulating the expression activity of antioxidant enzymes in vivo, thus exerting its inhibitory effect on tumor cells, which provides an idea for the molecular mechanism that natural products can indirectly exert their anticancer effect by regulating the activity of antioxidant enzymes.

At the same time, limonin down-regulated the expression of NQO1, indicating that limonin may indirectly act on the apoptosis pathway by regulating the expression activity of antioxidant enzymes in vivo, thus exerting its inhibitory effect on tumor cells, which provides an idea for the molecular mechanism that natural products can indirectly exert their anticancer effect by regulating the activity of antioxidant enzymes.

In order to explore the anticancer activity based on interaction between limonin and NQO1, Human promyelocytic leukemia cells (HL-60) were studied in vitro.

In order to explore the anticancer activity based on interaction between limonin and NQO1, Human promyelocytic leukemia cells (HL-60) were studied in vitro.

However, CAPE did not affect NLRP3 or IL-1beta transcription, but instead enhanced NLRP3 binding to ubiquitin molecules, promoting NLRP3 ubiquitination, and contributing to the anti-tumor effect in the AOM and DSS mouse model.

However, CAPE did not affect NLRP3 or IL-1beta transcription, but instead enhanced NLRP3 binding to ubiquitin molecules, promoting NLRP3 ubiquitination, and contributing to the anti-tumor effect in the AOM and DSS mouse model.

However, CAPE did not affect NLRP3 or IL-1beta transcription, but instead enhanced NLRP3 binding to ubiquitin molecules, promoting NLRP3 ubiquitination, and contributing to the anti-tumor effect in the AOM and DSS mouse model.

However, CAPE did not affect NLRP3 or IL-1beta transcription, but instead enhanced NLRP3 binding to ubiquitin molecules, promoting NLRP3 ubiquitination, and contributing to the anti-tumor effect in the AOM and DSS mouse model.

Thus, CAPE suppresses the interaction between NLRP3 and deubiquitinating enzymes, and enhances its interaction with a ubiquitin conjugating enzyme in vivo and in vitro, promoting NLRP3 ubiquitination.

Moreover, CAPE enhanced the binding of NLRP3 to ubiquitin molecules, promoted NLRP3 ubiquitination (XREF_FIG), and significantly blocked the formation of NLRP3 inflammasome, which were again reversed by rotenone (XREF_FIG).

CAPE Promotes NLRP3 Ubiquitination by Inhibiting ROS.

Moreover, CAPE enhanced the binding of NLRP3 to ubiquitin molecules, promoted NLRP3 ubiquitination (XREF_FIG), and significantly blocked the formation of NLRP3 inflammasome, which were again reversed by rotenone (XREF_FIG).

Moreover, CAPE significantly inhibited the formation of ASC dimers and reduced the abundance of NLRP3 inflammasome complexes in a dose dependent manner (XREF_FIG).

We first investigated whether CAPE inhibits the activation of NLRP3 inflammasome induced by ATP and LPS in macrophages in vitro.

CAPE Decreases NLRP3 Inflammasome Activation in BMDMs and THP-1 Cells.

We found that CAPE decreased NLRP3 inflammasome activation in BMDMs and THP-1 cells and protected mice from colorectal cancer induced by AOM and DSS.

In conclusion, CAC can be prevented by CAPE induced NLRP3 inflammasome inhibition, highlighting CAPE as a potential candidate for reducing the risk of CAC in patients with inflammatory bowel disease.

Overall, the results indicate that activated NLRP3 in AOM and DSS mouse model is suppressed by CAPE.

To determine whether CAPE inhibits NLRP3 inflammasome in vivo, we assessed NLRP3 expression in the AOM and DSS mouse model by immunohistochemistry and western blotting.

However, CAPE did not affect NLRP3 or IL-1beta transcription, but instead enhanced NLRP3 binding to ubiquitin molecules, promoting NLRP3 ubiquitination, and contributing to the anti-tumor effect in the AOM and DSS mouse model.

However, CAPE did not affect NLRP3 or IL-1beta transcription, but instead enhanced NLRP3 binding to ubiquitin molecules, promoting NLRP3 ubiquitination, and contributing to the anti-tumor effect in the AOM and DSS mouse model.

As shown in XREF_FIG, LPS + ATP promoted the expression of NLRP3 and pro-IL-1beta in THP-1 cells; however, real-time PCR revealed that after treatment with CAPE for 12 h, mRNA levels of NLRP3 and IL-1beta in THP-1 cells were similar to control (XREF_FIG), indicating that CAPE does not affect the transcription of NLRP3 and IL-1beta.

As shown in XREF_FIG, LPS + ATP promoted the expression of NLRP3 and pro-IL-1beta in THP-1 cells; however, real-time PCR revealed that after treatment with CAPE for 12 h, mRNA levels of NLRP3 and IL-1beta in THP-1 cells were similar to control (XREF_FIG), indicating that CAPE does not affect the transcription of NLRP3 and IL-1beta.

Moreover, CAPE decreased the mRNA levels of NLRP3, IL-1beta, IL-6, and TNF-alpha (XREF_FIG), increased the binding of NLRP3 to ubiquitin molecules and facilitated NLRP3 ubiquitination (XREF_FIG).

We then examined whether CAPE also reduces NLRP3 mRNA levels.

Altogether, these results indicate that CAPE reduces NLRP3 protein levels and suppresses NLRP3 activation in macrophages.

Western blotting showed that CAPE significantly inhibited the increased protein levels of NLRP3, caspase-1, and IL-1beta in BMDMs and THP-1 cells after LPS and ATP stimulation (XREF_FIG).

Furthermore, CAPE significantly reduced the expression of NLRP3, cleaved caspase-1, and cleaved IL-1beta, which was restored by rotenone (XREF_FIG).

CAPE enhanced the interaction between NLRP3 and Cullin1 and decreased the interaction between NLRP3 and CSN5 in THP-1 cells in a time dependent manner (XREF_FIG).

CAPE enhanced the interaction between NLRP3 and Cullin1 and decreased the interaction between NLRP3 and CSN5 in THP-1 cells in a time dependent manner (XREF_FIG).

Moreover, CAPE suppressed the interaction between NLRP3 and CSN5 but enhanced that between NLRP3 and Cullin1 both in vivo and in vitro.

NLRP3 interacts with ASC and pro-caspase-1 to form an inflammasome.

Altogether, these results indicate that CAPE reduces NLRP3 protein levels and suppresses NLRP3 activation in macrophages.

NLRP3 triggers innate immunity by activating caspase-1 and then cleaves immune and metabolic substrates, especially the pro inflammatory cytokine interleukin-1beta (IL-1beta), which induces inflammation and promotes tumor growth.

Activated NLRP3 promotes pro-caspase-1 proteolysis into its active form, caspase-1 (p20), and then cleaves pro-IL-1beta and pro-IL-18 into their mature forms (IL-1beta and IL-18).

Moreover, NLRP3 inhibition was found to prevent CAC.

Altogether, our findings indicate that inhibition of NLRP3 inflammasome by CAPE prevents CAC.

NLRP3 triggers innate immunity by activating caspase-1 and then cleaves immune and metabolic substrates, especially the pro inflammatory cytokine interleukin-1beta (IL-1beta), which induces inflammation and promotes tumor growth.

Altogether, our findings demonstrate that CAPE prevents CAC by post-transcriptionally inhibiting NLRP3 inflammasome.

Caffeic Acid Phenethyl Ester Prevents Colitis Associated Cancer by Inhibiting NLRP3 Inflammasome.

In this study, we provide evidence that CAPE facilitates NLRP3 ubiquitination by inhibiting ROS in THP-1 cells and inhibits enteritis and tumor burden by inhibiting NLRP3 in an AOM and DSS mouse model.

We first investigated whether CAPE inhibits the activation of NLRP3 inflammasome induced by ATP and LPS in macrophages in vitro.

We first investigated whether CAPE inhibits the activation of NLRP3 inflammasome induced by ATP and LPS in macrophages in vitro.

Lapatinib, the small molecule tyrosine kinase inhibitor which targets HER2 and EGFR, has considerable anti-tumor activity against HER2+ BC cells, including trastuzumab resistant cells.

Lapatinib, the small molecule tyrosine kinase inhibitor which targets HER2 and EGFR, has considerable anti-tumor activity against HER2+ BC cells, including trastuzumab resistant cells.

Given the fact that Lapatinib is a dual EGFR and HER2 inhibitor, we chose the HER2 overexpressing BC cell line, HCC-1954, and the EGFR overexpressing benign control cell line, MCF-10A, for further evaluation.

Given the fact that Lapatinib is a dual EGFR and HER2 inhibitor, we chose the HER2 overexpressing BC cell line, HCC-1954, and the EGFR overexpressing benign control cell line, MCF-10A, for further evaluation.

The knockdown of NLRP3 significantly reduces the proliferation, clonogenicity, invasion and migration in both Ishikawa and HEC-1A cells, while in contrast, NLRP3 overexpression enhances the proliferation, migration and invasion in both Ishikawa and HEC-1A cells and furthermore, increases caspase-1 activation and the release of IL-1beta in endometrial cancer cells.

Inhibition of NLRP3 suppresses the proliferation, migration and invasion, and promotes apoptosis in glioma cells, while in contrast, increased expression of NLRP3 significantly enhances the proliferation, migration and invasion as well as attenuating apoptosis in glioma cells (XREF_TABLE).

Similarly, NLRP3 expression levels are also correlated with the tumor size, lymph node metastatic status and IL-1beta expression in oral squamous cell carcinoma (OSCC), and downregulating NLRP3 expression markedly attenuates the proliferation, migration, and invasion of OSCC.

The knockdown of NLRP3 significantly reduces the proliferation, clonogenicity, invasion and migration in both Ishikawa and HEC-1A cells, while in contrast, NLRP3 overexpression enhances the proliferation, migration and invasion in both Ishikawa and HEC-1A cells and furthermore, increases caspase-1 activation and the release of IL-1beta in endometrial cancer cells.

Knockdown of NLRP3 suppresses UVB induced production of IL-1beta and attenuates other inflammatory mediators, such as IL-1alpha, IL-6, TNF-alpha and PGE 2.

The knockdown of NLRP3 significantly reduces the proliferation, clonogenicity, invasion and migration in both Ishikawa and HEC-1A cells, while in contrast, NLRP3 overexpression enhances the proliferation, migration and invasion in both Ishikawa and HEC-1A cells and furthermore, increases caspase-1 activation and the release of IL-1beta in endometrial cancer cells.

found that NLRP3 inhibits senescence and enables replicative immortality through regulating the Wnt and beta-catenin pathway via the thioredoxin interacting protein (TXNIP)/NLRP3 axis.

The knockdown of NLRP3 significantly reduces the proliferation, clonogenicity, invasion and migration in both Ishikawa and HEC-1A cells, while in contrast, NLRP3 overexpression enhances the proliferation, migration and invasion in both Ishikawa and HEC-1A cells and furthermore, increases caspase-1 activation and the release of IL-1beta in endometrial cancer cells.

Inhibition of NLRP3 suppresses the proliferation, migration and invasion, and promotes apoptosis in glioma cells, while in contrast, increased expression of NLRP3 significantly enhances the proliferation, migration and invasion as well as attenuating apoptosis in glioma cells (XREF_TABLE).

Consistently, knockdown of NLRP3 induces cell apoptosis in MCF-7 cells and decreases cell migration; nevertheless, in other cell-types, NLRP3 inflammasome may pharmacologically repress proliferation and metastasis of hepatic cell carcinoma (HCC) (XREF_TABLE).

found that NLRP3 overexpression inhibits cell proliferation and stimulates apoptosis in leukemic cells.

Similarly, NLRP3 expression levels are also correlated with the tumor size, lymph node metastatic status and IL-1beta expression in oral squamous cell carcinoma (OSCC), and downregulating NLRP3 expression markedly attenuates the proliferation, migration, and invasion of OSCC.

NLRP3 inflammasome inactivation, driven by miR-223-3p, increases proliferation, promotes invasion and inhibits apoptosis in breast cancer cells.

The attenuation of the NLRP3 downstream pyroptosis pathway promotes apoptosis.

Consistently, knockdown of NLRP3 induces cell apoptosis in MCF-7 cells and decreases cell migration; nevertheless, in other cell-types, NLRP3 inflammasome may pharmacologically repress proliferation and metastasis of hepatic cell carcinoma (HCC) (XREF_TABLE).

Similarly, activation of NLRP3 inflammasome in mesothelial cells of lung cancer leads to an inflammatory response that fuels cancer initiation and progression and then activates the NF-kappaB-signaling pathway in lung cancer, consequently increasing proliferation and inhibiting apoptosis.

NLRP3 inflammasomes mediate both suppressions of apoptosis and progression of the cell cycle by leptin dependent ROS production in breast cancer, which is mediated via estrogen receptor alpha (ERalpha)/reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase signaling.

proposed that significant cell death was observed only when P2X7R and NLRP3 inflammasome were both inhibited by ATP and MCC950, a specific inhibitor of NLRP3 inflammasome, and further research into safety manipulation of NLRP3 inflammasome without enhancing significant dose dependent side effects is required.

In addition, inactivation of NLRP3 inflammasome has also been found to reduce IL-1beta expression and halt development of melanoma.

Inactivation of NLRP3 inflammasome driven by miR-233-3p has been found to decrease the expression of NLRP3 inflammasome associated proteins, ASC, IL-1beta, and IL-18 in breast cancers and suppress tumor growth.

found that NLRP3 in renal tubular cells re-localizes from the cytosol to the mitochondria during hypoxia and binds to MAVS, which attenuates mtROS production and depolarization of the mitochondrial membrane potential under hypoxia.

Huang et al. reported that beta-catenin promotes NLRP3 inflammasome activation, and silencing of beta-catenin impairs NLRP3 activation.

TXNIP knockdown or targeting by miR-20b resulted in a pro tumorigenic phenotype with increased cell proliferation, inhibited cell senescence reduced cell cycle modulators (p16 and p21), and decreased NLRP3 inflammasome associated proteins (NLRP3 and cleaved caspase-1).

In contrast, overexpression of NLRP3 enhances the activities of proliferation, migration and invasion as well as increasing caspase-1 activation and IL-1beta secretion in human endometrial cancer cells.

Moreover, the silencing of NLRP3 significantly decreases the migration and invasion in OSCC cells and reduces EMT related protein expression.

The knockdown of NLRP3 significantly reduces the proliferation, clonogenicity, invasion and migration in both Ishikawa and HEC-1A cells, while in contrast, NLRP3 overexpression enhances the proliferation, migration and invasion in both Ishikawa and HEC-1A cells and furthermore, increases caspase-1 activation and the release of IL-1beta in endometrial cancer cells.

NLRP3 inflammasome inactivation, driven by miR-223-3p, increases proliferation, promotes invasion and inhibits apoptosis in breast cancer cells.

The role of NLRP3 in promoting invasion has been demonstrated with human endometrial cancer cell lines such as Ishikawa and HEC-1A cells, where knockdown of NLRP3 significantly reduces proliferation, clonogenicity, invasion and migration.

Increased activation of the NLRP3 inflammasome promotes migration and invasion activities in gastric cancer cells.

NLRP3 in the primary lesion of cancer cells drives the production of pro-IL-1beta, DC maturation, and the secretion of IL-1beta to support the evolution of tumor specific CD8 + T cells.

In the primary lesion of cancer cells, NLRP3 drives the production of pro-IL-1beta, DC maturation, and the secretion of IL-1beta to support the differentiation of tumor specific CD8 + T cells.

In contrast, overexpression of NLRP3 enhances the activities of proliferation, migration and invasion as well as increasing caspase-1 activation and IL-1beta secretion in human endometrial cancer cells.

NLRP3 enhances IL-1beta, subsequently activating NF-kappaB, and initiates JNK signaling to cause proliferation and invasion in gastric cancer.

NLRP3 agonist induces Wnt and beta-catenin activation, whereas inactivation of Wnt and beta-catenin results in the inhibition of NLRP3, IL-1beta.

NLRP3 inflammasome activation induced IL-1beta and IL-18 in lung cancer may work through mechanisms other than the caspase-1 pathway, indicating that NLRP3 inflammasome can mediate the release of IL-1beta and IL-18 through caspase-1-dependent or -independent pathways.

Epistasis analysis revealed that NLRP3 variants together with polymorphisms in inflammasome related genes modulate both the frequency of inflammasome activation and the process of IL-1beta and IL-18 maturation thatinfluence HPV infection outcome and cervical cancer progression (XREF_TABLE).

NLRP3 in the primary lesion of cancer cells drives the production of pro-IL-1beta, DC maturation, and the secretion of IL-1beta to support the evolution of tumor specific CD8 + T cells.

In the primary lesion of cancer cells, NLRP3 drives the production of pro-IL-1beta, DC maturation, and the secretion of IL-1beta to support the differentiation of tumor specific CD8 + T cells.

NLRP3 inflammasome activation induced IL-1beta and IL-18 in lung cancer may work through mechanisms other than the caspase-1 pathway, indicating that NLRP3 inflammasome can mediate the release of IL-1beta and IL-18 through caspase-1-dependent or -independent pathways.

Epistasis analysis revealed that NLRP3 variants together with polymorphisms in inflammasome related genes modulate both the frequency of inflammasome activation and the process of IL-1beta and IL-18 maturation thatinfluence HPV infection outcome and cervical cancer progression (XREF_TABLE).

In contrast, overexpression of NLRP3 enhances the activities of proliferation, migration and invasion as well as increasing caspase-1 activation and IL-1beta secretion in human endometrial cancer cells.

Consistently, knockdown of NLRP3 induces cell apoptosis in MCF-7 cells and decreases cell migration; nevertheless, in other cell-types, NLRP3 inflammasome may pharmacologically repress proliferation and metastasis of hepatic cell carcinoma (HCC) (XREF_TABLE).

The role of NLRP3 in promoting invasion has been demonstrated with human endometrial cancer cell lines such as Ishikawa and HEC-1A cells, where knockdown of NLRP3 significantly reduces proliferation, clonogenicity, invasion and migration.

In contrast, overexpression of NLRP3 enhances the activities of proliferation, migration and invasion as well as increasing caspase-1 activation and IL-1beta secretion in human endometrial cancer cells.

The knockdown of NLRP3 significantly reduces the proliferation, clonogenicity, invasion and migration in both Ishikawa and HEC-1A cells, while in contrast, NLRP3 overexpression enhances the proliferation, migration and invasion in both Ishikawa and HEC-1A cells and furthermore, increases caspase-1 activation and the release of IL-1beta in endometrial cancer cells.

NLRP3 inflammasome inactivation, driven by miR-223-3p, increases proliferation, promotes invasion and inhibits apoptosis in breast cancer cells.

Similarly, activation of NLRP3 inflammasome in mesothelial cells of lung cancer leads to an inflammatory response that fuels cancer initiation and progression and then activates the NF-kappaB-signaling pathway in lung cancer, consequently increasing proliferation and inhibiting apoptosis.

We suggest the opposite results in NLRP3 mediated cell proliferation due to different IL-1beta levels (XREF_TABLE).

Despite the major downstream event of NLRP3 inflammation formation of caspase-1 mediated pyroptosis, NLRP3 seems to mediate the dual-function of apoptosis and survival.

Inhibition of NLRP3 suppresses the proliferation, migration and invasion, and promotes apoptosis in glioma cells, while in contrast, increased expression of NLRP3 significantly enhances the proliferation, migration and invasion as well as attenuating apoptosis in glioma cells (XREF_TABLE).

found that NLRP3 overexpression inhibits cell proliferation and stimulates apoptosis in leukemic cells.

NLRP3 in the primary lesion of cancer cells drives the production of pro-IL-1beta, DC maturation, and the secretion of IL-1beta to support the evolution of tumor specific CD8 + T cells.

In the primary lesion of cancer cells, NLRP3 drives the production of pro-IL-1beta, DC maturation, and the secretion of IL-1beta to support the differentiation of tumor specific CD8 + T cells.