Role of Interleukin-1 in the pathogenesis of colorectal cancer: A brief look at anakinra therapy

Xie, Jun; Zhang, Yu; Lei, Jiang

doi:10.1016/j.intimp.2022.108577

Cited by 7 publications

(4 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This study found that inflammasome activation reduced the secretion of IFNg and CXCL10. The loss of IFN-γ secretion and IFN-γ inducible protein, CXCL10, induces the expression of cellular FLICE-like inhibitory protein (cFLIPL) and mixed lineage kinase domain-like (MLKL) [ 11 , 44 ]. cFLIPL and MLKL expression could promote necroptosis, leading to CRC recurrence [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

“…Based on the role of the inflammasome in the pathogenesis of cancer, therapeutic approaches aimed to inhibit the NLRP3-induced proinflammatory cytokines were tested [ 9 ]. Recently, an IL-1β receptor antagonist, anakinra, administered alone was found to be insufficient in reducing tumor size in cancers, including CRC [ 10 , 11 ]. In addition to IL-1β receptor antagonists, the function of NLRP3 could be suppressed by inactivating caspase-1, blocking the formation of the inflammasome complex, or inhibiting the upstream signals [ 5 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Implications of NLRP3 Suppression Using Glibenclamide and miR-223 against Colorectal Cancer

Hamza,

Garanina,

Shkair

et al. 2024

Pharmaceuticals

View full text Add to dashboard Cite

The NLR family pyrin domain containing 3 (NLRP3) promotes the growth of colorectal cancer (CRC). However, the therapeutic effect of NLRP3 inhibition on CRC cell progression is controversial. This study comparatively investigated the therapeutic effect of a pharmacological NLRP3 inhibitor, glibenclamide (gli), and the post-translational suppression of NLRP3 by miR-223 on CRC cell progression in HCT-116 and HCT-15 cells. LPS and ATP were used to activate Gli-treated and LSB-hsa-miR-223-3p (WTmiR-223)-expressing HCT-116 cells. NLRP3.AB.pCCL.sin.cPPT.U6.miR-223-Decoy.hPGK.GFP.WPRE plasmid (DmiR-223) was the negative control for miR-223 expression. NLRP3, gasdermin D, and BAX expressions were analyzed using western blotting. Real-time PCR detected the RNA expression of autophagy-related genes ATG5, BECN1, and miR-223 in non-transfected cells. ELISA analyzed IL-1β and IL-18 in the medium. MTS-1, annexin V, wound-healing, and sphere-invasion assays were used to assess cell viability and progression. A multiplex cytokine assay detected proinflammatory cytokine secretion. LPS–ATP-activated NLRP3 produced gasdermin D cleavage, released IL-1b and IL-18, and activated cell migration and sphere invasion. In contrast, reduced cell growth, miR-223 expression, IFN-γ, CXCL10, and LIF secretion were found in cells after inflammasome activation. Both gli and WTmiR-223 induced autophagy genes ATG5 and BECN1 and reduced the NLRP3 activation and its downstream proteins. However, while gli had a limited effect on the production of IFN-γ, CXCL10, and LIF, WTmiR-223 increased the release of those cytokines. In addition, gli did not suppress cell growth, while WTmiR-223 promoted apoptosis. Notably, neither gli nor WTmiR-223 effectively prevented sphere invasion. These data suggest that, while WTmiR-223 could have a better anticancer effect in CRC compared to gli, the sole usage of miR-223-mediated NLRP3 suppression may not be sufficient to prevent CRC metastasis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Implications of NLRP3 Suppression Using Glibenclamide and miR-223 against Colorectal Cancer

Hamza,

Garanina,

Shkair

et al. 2024

Pharmaceuticals

View full text Add to dashboard Cite

show abstract

“…A rather interesting notion in the recent literature is that blocking the IL-1 pathway may be a therapeutic option in malignancy, e.g., colorectal and breast cancer [ 97 , 98 ]. In an analysis of the CANTOS trial, incident new lung cancer diagnosis, lung, and total cancer mortality were significantly lower in the canakinumab-treated population compared to placebo, suggesting that the anti-inflammatory effect of blocking IL-1β innate immunity may protect from the development of lung cancer [ 99 ].…”

Section: Use Of Il-1 Blockers In Specific Clinical Scenariosmentioning

confidence: 99%

Interleukin-1 Blockers: A Paradigm Shift in the Treatment of Recurrent Pericarditis

Lazarou,

Koutsianas,

Theofilis

et al. 2024

Life

View full text Add to dashboard Cite

Recurrent pericarditis is a problematic clinical condition that impairs the quality of life of the affected patients due to the need for repeated hospital admissions, emergency department visits, and complications from medications, especially glucocorticoids. Unfortunately, available treatments for recurrent pericarditis are very limited, including only a handful of medications such as aspirin/NSAIDs, glucocorticoids, colchicine, and immunosuppressants (such as interleukin-1 (IL-1) blockers, azathioprine, and intravenous human immunoglobulins). Until recently, the clinical experience with the latter class of medications was very limited. Nevertheless, in the last decade, experience with IL-1 blockers has consistently grown, and valid clinical data have emerged from randomized clinical trials. Accordingly, IL-1 blockers are a typical paradigm shift in the treatment of refractory recurrent pericarditis with a clearly positive cost/benefit ratio for those unfortunate patients with multiple recurrences. A drawback related to the above-mentioned medications is the absence of universally accepted and established treatment protocols regarding the full dose administration period and the need for a tapering protocol for individual medications. Another concern is the need for long-standing treatments, which should be discussed with the patients. The above-mentioned unmet needs are expected to be addressed in the near future, such as further insights into pathophysiology and an individualized approach to affected patients.

show abstract

“…Cytokines are multifunctional immune system mediators that play a role in both pro-and anti-inflammatory immune responses. Interleukin-1 (IL-1) is a member of an 11-member family that plays a role in inflammatory reactions [4]. IL-1 is generated and secreted by a variety of cell types inside the tumor, including immune cells, fibroblasts and cancer cells [5].…”

Section: Introductionmentioning

confidence: 99%

Melittin, A Potential Natural Toxin with Anticancer Properties: Regulating IL-1β, COX-2 and TNF-α in Human Colorectal Cancer Cells WiDr

Plasay,

Muslimin

2024

Trends Sci

View full text Add to dashboard Cite

Despite decades of study, the antiproliferation and molecular processes of the biomolecular elements of honeybee venom (i.e., melittin) as anticancer agents remain largely unclear. This study illustrated the antiproliferation effect of melittin by regulating IL-1β, COX-2 and TNF-α in human colorectal cancer cells WiDr. In order to assess the antiproliferation, various concentrations of melittin were contacted to the WiDr cell through MTT assay. Moreover, the ability of melittin to regulate the expression of IL-1β, COX-2 and TNF-α was determined by ELISA. The cytotoxic effect showed the inhibition of the WiDr cell in a dose-dependent manner, with the IC10, IC25 and IC50 values of 0.095 ± 0.001, 0.147 ± 0.002 and 0.207 ± 0.004, respectively. Additionally, in further investigations, melittin markedly inhibited the IL-1β and COX-2 expression but induced the TNF-α, demonstrating significant (p < 0.05) elevations compared to the control group. These findings point to the antiproliferative properties of melittin in WiDr cells. Therefore, as a unique natural treatment for colorectal cancer, melittin may have a lot of potential. HIGHLIGHTS In this study, we confirmed melittin has very strong anticancer activity against colorectal cell cancer cells with IC50 values of 0.207 ± 0.004 µM Melittin regulates colorectal cell cancer by inhibiting the IL-1β and COX-2 expression Melittin increases the expression of TNF-α to inhibit colorectal cell cancer GRAPHICAL ABSTRACT

show abstract

Role of Interleukin-1 in the pathogenesis of colorectal cancer: A brief look at anakinra therapy

Cited by 7 publications

References 112 publications

Implications of NLRP3 Suppression Using Glibenclamide and miR-223 against Colorectal Cancer

Implications of NLRP3 Suppression Using Glibenclamide and miR-223 against Colorectal Cancer

Interleukin-1 Blockers: A Paradigm Shift in the Treatment of Recurrent Pericarditis

Melittin, A Potential Natural Toxin with Anticancer Properties: Regulating IL-1β, COX-2 and TNF-α in Human Colorectal Cancer Cells WiDr

Contact Info

Product

Resources

About