NLRP3 Inflammasome Activation Inhibitors in Inflammation-Associated Cancer Immunotherapy: An Update on the Recent Patents

Kopalli, Spandana Rajendra; Kang, Tae-Bong; Lee, Kwang-Ho; Koppula, Sushruta

doi:10.2174/1574892812666171027102627

Cited by 20 publications

(15 citation statements)

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“…Clearly, NLRP3 inflammasome activation performed a dual role in cancers . Reports indicated that activated NLRP3 inflammasome contributed to the matastasis of breast cancer and the progression of late stage of melanoma, but it acted as a negative regulator in human hepatocellular carcinoma and colorectal cancer . In our present study, NLRP3 inflammasome activation was demonstrated to play an important role in promoting inflammation‐related lung cancer in vitro, this result was supported by previous studies that NLRP3 inflammasome was upregulated in lung adenocarcinoma and small cell lung cancer in vivo .…”

Section: Discussionsupporting

confidence: 89%

“…Together, these data confirmed that NLRP3 inflammasome activation could be enhanced in the cells upon LPS + CTPE exposure than that in the cells exposed to CTPE alone, indicating that NLRP3 inflammasome‐mediated IL‐1β signal was involved in the development of inflammation‐related lung cancer. Clearly, NLRP3 inflammasome activation performed a dual role in cancers . Reports indicated that activated NLRP3 inflammasome contributed to the matastasis of breast cancer and the progression of late stage of melanoma, but it acted as a negative regulator in human hepatocellular carcinoma and colorectal cancer .…”

Section: Discussionmentioning

confidence: 99%

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NLRP3 inflammasome activation involved in LPS and coal tar pitch extract‐induced malignant transformation of human bronchial epithelial cells

Duan

Wang

Huang

et al. 2019

Environmental Toxicology

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Inflammatory microenvironment has been found as a new characteristic of cancer; however, the mechanisms of inflammation-related lung cancer remain unclear. To explore the role of NLRP3 inflammsome activation in inflammation-related lung carcinogenesis, a cell model was set up. Human bronchial epithelial cells (BEAS-2B) were stimulated with 1 μg/mL lipopolysaccharide (LPS) for 24 hours, and then treated with 2.4 μg/mL coal tar pitch extract (CTPE) for 24 hours, after removal of LPS and CTPE, the cells were numbered passage 1 and were passaged and treated in this way until passage 30, which was called LPS + CTPE group. DMSO and Saline were used as vehicle controls. Malignant transformation of cells in passage 30 was evaluated by morphological change, platelet clone formation assay, and tumor formation in nude mice. The mRNA levels of NLRP3 and IL-1β were detected by real time-PCR. The combination of NLRP3 and caspase-1 were determined using immunofluorescence and confocal. The protein expression of NLRP3, cleaved caspase-1(p10), and cleaved IL-1β was detected using Western blot. It was shown that CTPE, LPS + CTPEstimulated BEAS-2B cells of passage 30 changed a lot morphologically. The clone formation rates, the rates of positive cells of NLRP3 and caspase-1 combination, the mRNA levels of NLRP3 and IL-1β, the protein expression of NLRP3, cleaved caspase-1(p10) and cleaved IL-1β of cells exposed with CTPE and LPS + CTPE at passage 30 were significantly increased compared to vehicle controls. Furthermore, the ability of tumor formation in nude mice, the rates of clone formation and positive cells, mRNA and protein levels of NLRP3 inflammasome activation-related factors in LPS + CTPE-induced cells were all higher than those in cells stimulated with CTPE alone. In conclusion, the cell model of inflammation-related lung cancer is set up successfully, and NLRP3 inflammasome activation may be involved in the malignant transformation of BEAS-2B cells which induced by CTPE alone or LPS combined with CTPE.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

NLRP3 inflammasome activation involved in LPS and coal tar pitch extract‐induced malignant transformation of human bronchial epithelial cells

Duan

Wang

Huang

et al. 2019

Environmental Toxicology

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“…72 NLRP3 inflammasome polymorphisms are also associated with the development of certain cancers, including breast cancer, melanoma, and hepatocellular carcinoma (HCC), 73 and NLRP3 inflammasome inhibitors have been patented for potential cancer therapeutic applications. 74 The NLRP3 inflammasome is a multi-subunit cytosolic protein complexes that assembles upon exposure of its pattern recognition receptor, NLRP3, to a broad range of damage-associated molecular patterns or responses induced by them, including extracellular adenosine triphosphate (ATP), crystalline complexes and protein aggregates, mitochondrial dysfunction and lysosomal damage. 75 Assembly of the NLRP3 inflammasome complex forms a scaffold that induces the activation of procapase-1 to catalyze the maturation of IL-1β and IL-18, which promote recruitment of immune cells and enhance the activity of natural killer (NK) and T-cells, to stimulate a localized proinflammatory environment.…”

Section: Inflammationmentioning

confidence: 99%

“…However, recent work suggests that increased NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome activity, which plays a key role in innate immunity, can regulate EV secretion, with several reports demonstrating direct associations between NLRP3 inflammasome activation and enhanced exosome release rates and changes in exosome cargo compositions . NLRP3 inflammasome polymorphisms are also associated with the development of certain cancers, including breast cancer, melanoma, and hepatocellular carcinoma (HCC), and NLRP3 inflammasome inhibitors have been patented for potential cancer therapeutic applications …”

Section: Introductionmentioning

confidence: 99%

Tumor‐derived exosomes (TDEs): How to avoid the sting in the tail

Wan

Ning

Spiegel

et al. 2019

Medicinal Research Reviews

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Exosomes are abundantly secreted extracellular vesicles that accumulate in the circulation and are of great interest for disease diagnosis and evaluation since their contents reflects the phenotype of their cell of origin. Tumor‐derived exosomes (TDEs) are of particular interest for cancer diagnosis and therapy, since most tumor demonstrate highly elevated exosome secretion rates and provide specific information about the genotype of a tumor and its response to treatment. TDEs also contain regulatory factors that can alter the phenotypes of local and distant tissue sites and alter immune cell functions to promote tumor progression. The abundance, information content, regulatory potential, in vivo half‐life, and physical durability of exosomes suggest that TDEs may represent a superior source of diagnostic biomarkers and treatment targets than other materials currently under investigation. This review will summarize current information on mechanisms that may differentially regulate TDE biogenesis, TDE effects on the immune system that promote tumor survival, growth, and metastasis, and new approaches understudy to counteract or utilize TDE properties in cancer therapies.

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“…Genetic polymorphisms involved with the NLRP3 inflammasome were linked to various diseases, such as rheumatoid arthritis, ankylosing spondylitis, melanoma, liver cancer, lung cancer, and ovarian cancer [7–9]. Meanwhile, a truncating polymorphism (rs2043211) can produce a nonfunctional CARD8 and induce an amplification of the inflammatory process, or even evolve into cancer [4].…”

Section: Introductionmentioning

confidence: 99%

The Genetic Polymorphisms of NLRP3 Inflammasome Associated with T Helper Cells in Patients with Multiple Myeloma

Zhao

Hua

Yan

et al. 2018

Journal of Immunology Research

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The pathogenesis of multiple myeloma (MM) remains unclear and the NLRP3 inflammasome has been more and more recognized in the progression of many diseases. To investigate the role of the NLRP3 inflammasome in MM, we determined the genetic polymorphisms and expression of NLRP3 inflammasome-related genes (IL-1β, IL-18, CARD8, and NF-κB) in MM patients, and explored their clinical relevance. Furthermore, we investigated the relationship of the NLRP3 inflammasome with Th cells in MM. Our study showed that the CARD8-C10X (rs2043211) AT genotype contributed to the susceptibility of MM. CARD8-C10X TT patients had earlier clinical stage. The WBC count in the three CARD8 genotypes showed an increasing trend (AA

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NLRP3 Inflammasome Activation Inhibitors in Inflammation-Associated Cancer Immunotherapy: An Update on the Recent Patents

Abstract: The vigorous effort to discover and develop agents to specifically inhibit NLRP3 inflammasome activation, may pave the way to therapeutic intervention targeting inflammasome-regulated pathways that are involved in the pathogenesis of various forms of cancer.

Cited by 20 publications

References 0 publications

NLRP3 inflammasome activation involved in LPS and coal tar pitch extract‐induced malignant transformation of human bronchial epithelial cells

NLRP3 inflammasome activation involved in LPS and coal tar pitch extract‐induced malignant transformation of human bronchial epithelial cells

Tumor‐derived exosomes (TDEs): How to avoid the sting in the tail

The Genetic Polymorphisms of NLRP3 Inflammasome Associated with T Helper Cells in Patients with Multiple Myeloma

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