Inflammasome inhibitors: promising therapeutic approaches against cancer

Xu, Shengchao; Li, Xizhe; Liu, Yuanqi; Xia, Yu; Chang, Ruimin; Zhang, Chunfang

doi:10.1186/s13045-019-0755-0

Cited by 69 publications

(53 citation statements)

References 139 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Inflammation, one of the major hallmarks of cancer, mediates cancer progression via the coordinated actions of cytokines, chemokines, and innate immune cells [16]. Inflammasomes, cytosolic multiprotein oligomers containing a member of the NOD-like receptor protein (NLRP) family, the apoptosis-associated speck-like protein containing a CARD (ASC), and pro-caspase-1, are responsible for producing active interleukin family cytokines in response to infection and cellular stress [17].…”

Section: Introductionmentioning

confidence: 99%

Globular Adiponectin Inhibits Breast Cancer Cell Growth through Modulation of Inflammasome Activation: Critical Role of Sestrin2 and AMPK Signaling

Pham

Raut

Pandit

et al. 2020

Cancers

View full text Add to dashboard Cite

Adiponectin, an adipokine predominantly derived from adipose tissue, exhibits potent antitumor properties in breast cancer cells. However, its mechanisms of action remain elusive. Inflammasomes—intracellular multimeric protein complexes—modulate cancer cell growth in a complicated manner, as well as playing a role in the innate immune system. Herein, we examined the potential role of inflammasomes in the antitumor activity of adiponectin and found that globular adiponectin (gAcrp) significantly suppressed inflammasomes activation in breast cancer cells both in vitro and in vivo conditions, as determined by decreased expression of inflammasomes components, including NOD-like receptor pyrin domain-containing protein 3 (NLRP3) and the apoptosis-associated speck-like protein containing a CARD (ASC), and inhibition of interleukin-1β and caspase-1 activation. Treatment with pharmacological inhibitors of inflammasomes caused decrease in cell viability, apoptosis induction, and G0/G1 cell cycle arrest, suggesting that inflammasomes activation is implicated in the growth of breast cancer cells. In addition, treatment with gAcrp generated essentially similar results to those of inflammasomes inhibitors, further indicating that suppression of breast cancer cell growth by gAcrp is mediated via modulation of inflammasomes. Mechanistically, gAcrp suppressed inflammasomes activation through sestrin2 (SESN2) induction, liver kinase B1 (LKB-1)-dependent AMP-activated protein kinase (AMPK) phosphorylation, and alleviation of endoplasmic reticulum (ER) stress. Taken together, these results demonstrate that gAcrp inhibits growth of breast cancer cells by suppressing inflammasomes activation, at least in part, via SESN2 induction and AMPK activation-dependent mechanisms.

show abstract

Section: Introductionmentioning

confidence: 99%

Globular Adiponectin Inhibits Breast Cancer Cell Growth through Modulation of Inflammasome Activation: Critical Role of Sestrin2 and AMPK Signaling

Pham

Raut

Pandit

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…In our previous study, we indicated that the inflammasome may play an important role in non-bacterial prostate inflammation [8], as also suggested in other studies [9][10][11]. In addition, the inflammasome has gradually become a target for treating pain [12] and inflammation [13,14]. However, there is still no definitive treatment targeting the inflammasome in CPPS.…”

Section: Introductionmentioning

confidence: 52%

Beneficial Effects of Inflammatory Cytokine-Targeting Aptamers in an Animal Model of Chronic Prostatitis

Chang

Lin

et al. 2020

IJMS

View full text Add to dashboard Cite

Non-bacterial prostatitis is an inflammatory disease that is difficult to treat. Oligonucleotide aptamers are well known for their stability and flexibility in conjugating various inflammatory molecules. In this study, we investigated the effects of inflammatory cytokine-targeting aptamers (ICTA), putative neutralizers of TNF-alpha and IL-1 beta activation, on local carrageenan-induced prostate inflammation, allodynia, and hyperalgesia in rats. In vitro evaluation confirmed the binding capability of ICTA. Intraprostatic injection of carrageenan or control vehicle was performed in six-week-old rats, and ICTA (150 µg) or vehicle was administered in the prostate along with carrageenan injection. The von Frey filament test was performed to determine mechanical allodynia, and prostate inflammation was examined seven days after drug administration. Local carrageenan administration resulted in a reduction of the tactile threshold. The levels of mononuclear cell infiltration, pro-inflammatory cytokine interleukin-1 beta (b), caspase-1 (casp-1), and Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing proteins 1 and 3 (NALP1 and NALP3) in the prostate of rats were increased seven days after carrageenan injection. Treatment with ICTA significantly attenuated the carrageenan-induced hyperalgesia and reduced the elevated levels of proteins including TNF-a and IL-1b in the rats. Apoptosis markers, B-cell lymphoma 2-associated X protein (Bax) and caspase-3, were elevated in ICTA-treated Chronic pelvic pain syndrome (CPPS) rats. These results suggest that ICTA provides protection against local carrageenan-induced enhanced pain sensitivity, and that the neutralization of proinflammatory cytokines may result in inflammatory cell apoptosis.

show abstract

“…Moreover, Yang et al con rmed that CRP promoted myeloma cell proliferation under stress and protected cancer cells from being damaged by chemotherapy drugs [48]. What's more, Shengchao Xu et al demonstrated that in ammasome inhibitors are helpful in the treatment of in ammationrelated tumors [49]. Clearly, the mechanisms of CRP regarding the progression of B-iNHL need to be clari ed in further investigations.…”

Section: Discussionmentioning

confidence: 99%

The Value of C-Reactive Protein, C-Reactive Protein Kinetics and C-reactive Protein to Albumin Ratio on Prognosis in Newly Diagnosed Indolent B-cell Non-Hodgkin Lymphoma

Zhang¹,

Zhou²,

Sun³

et al. 2020

Preprint

View full text Add to dashboard Cite

Objective: This study aimed to determine prognostic significance of C-reactive protein (CRP), CRP kinetics and CRP to albumin ratio (CAR) in indolent B-cell non-Hodgkin lymphoma (B-iNHL) patients. Methods: The association among these blood makers and overall survival (OS), disease-free survival (DFS), progression-free survival (PFS) were analyzed in 243 B-iNHL patients. OS, DFS and PFS were determined by Kaplan–Meier curves. Cox proportional analysis was performed to examine the prognostic significance of clinicopathological variables. Results: Multivariate analyses identified that elevated pretreatment CRP (HR: 5.110, 95% CI: 1.904-13.717, p=0.001), post-treatment CRP (HR: 5.826, 95% CI: 1.659-20.458, p=0.006), continuously elevated CRP (HR: 6.461, 95% CI: 2.620-15.930, p<0.001) and elevated CAR (HR: 3.768, 95% CI: 1.415-10.034, p=0.008) had association with worse OS. Likewise, elevated pretreatment CRP (HR: 3.767, 95% CI: 1.777-7.984, p=0.001), post-treatment CRP (HR: 2.384, 95% CI: 1.027-5.534, p=0.043), ever-elevated CRP (HR: 2.425, 95% CI: 1.105-5.322, p=0.027), continuously elevated CRP (HR: 4.748, 95% CI: 2.114-10.660, p<0.001) and elevated CAR (HR: 2.824, 95% CI: 1.336-5.971, p=0.007) were in independent significance with worse DFS. Elevated pretreatment CRP (HR: 2.606, 95% CI: 1.338-5.076, p=0.005), ever-elevated CRP (HR: 2.086, 95% CI: 1.040-4.188, p=0.039), continuously elevated CRP (HR: 3.296, 95% CI: 1.594-6.818, p=0.001) and elevated CAR (HR: 1.991, 95% CI: 1.021-3.882, p=0.043) were determined in independent significance with poor PFS. The effect was statistically significant in both follicular lymphoma (FL) and chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/ SLL) patients.Conclusions: In conclusion, we demonstrate that CRP level, CRP kinetics and CAR could be potential prognostic indicators with independent significance in patients with B-iNHL, also in FL and CLL/ SLL subgroups. CRP and CAR make an implementation for prognostic evaluation more easily and effectively in B-iNHL patients.

show abstract

Inflammasome inhibitors: promising therapeutic approaches against cancer

Cited by 69 publications

References 139 publications

Globular Adiponectin Inhibits Breast Cancer Cell Growth through Modulation of Inflammasome Activation: Critical Role of Sestrin2 and AMPK Signaling

Globular Adiponectin Inhibits Breast Cancer Cell Growth through Modulation of Inflammasome Activation: Critical Role of Sestrin2 and AMPK Signaling

Beneficial Effects of Inflammatory Cytokine-Targeting Aptamers in an Animal Model of Chronic Prostatitis

The Value of C-Reactive Protein, C-Reactive Protein Kinetics and C-reactive Protein to Albumin Ratio on Prognosis in Newly Diagnosed Indolent B-cell Non-Hodgkin Lymphoma

Contact Info

Product

Resources

About