Involvement of inflammasomes in tumor microenvironment and tumor therapies

Zhang, Ziqi; Li, Xue; Wang, Yang; Wei, Yuquan; Wei, Xiawei

doi:10.1186/s13045-023-01407-7

Journal of Hematology & Oncology

Table 2 Preclinical research works about inflammasome interventions

From: Involvement of inflammasomes in tumor microenvironment and tumor therapies

Type of interventions	Agents	Type of diseases	Outcomes	References
NLRP3 inhibitor	MCC950	Colorectal carcinoma	MCC950 reverses FL118-induced pyroptosis	[216]
		Pancreatic cancer	MCC950 abrogates NLRP3/caspase-1/IL-1β-mediated cell proliferation	[159]
		Head and neck squamous cell carcinoma	MCC950 reduces MDSCs, Tregs, and TAMs while increasing CD4⁺ and CD8⁺ T cells in TME where NLRP3 is overexpressed	[203]
	BAY 11–7082	T cell leukemia	Apoptosis is induced in T cell leukemia cells by BAY 11–7082 through inhibiting NF-κB	[297]
		Gastric cancer	Apoptosis is induced in gastric cancer cells by BAY 11–7082 through inhibiting NF-κB	[298]
		Lupus nephritis	Lupus nephritis is attenuated by BAY 11–7082 through inhibiting both NLRP3 and NF-κB	[299]
		Psoriasis	BAY 11–7082 protects animal models from psoriasis through inhibiting both NLRP3 and NF-κB	[300]
	ACT001	Parkinson’s disease	ACT001 ameliorates NLRP3-mediated neuroinflammation in animal models of Parkinson’s disease	[260]
	Isoliquiritigenin	Diet-induced insulin resistance	Isoliquiritigenin inhibits diet-induced insulin resistance through inhibiting NLRP3 activation	[256]
	Tranilast	Gouty arthritis, cryopyrin-associated autoinflammatory syndromes, and type 2 diabetes	Tranilast shows preventive or therapeutic efficacy in three mouse models of NLRP3-related diseases	[250]
		Atherosclerosis	Tranilast dampens the initiation and progression of atherosclerosis through enhancing NLRP3 ubiquitination	[301]
		NSCLC	Tranilast inhibits EMT invasion, and metastasis of lung cancer cell lines	[252]
		Gastric cancer	Tranilast blocks interaction between mesothelial cells and cancer cells resulting in diminished tumor growth and fibrosis	[253]
	OLT1177	Melanoma	OLT1177 disrupts IL-1β/IL-6/STAT3 axis in tumor cells and reduces immunosuppressive activities in MDSCs	[202]
		Melanoma	OLT1177 reduces MDSCs expansion and tumor growth, whose effects could be further improved in combination with anti-PD-1	[245]
		Alzheimer’s disease	OLT1177 reduces the number of plaques in cortex and rescues cognitive impairment	[302]
		Allergic asthma	Both i.p. and oral treatment of OLT1177 alleviate allergic asthma	[303]
	CY-09	Breast cancer	CY-09 curbs NLRP3-mediated drug resistance and EMT	[218]
		Diet-induced hepatic steatosis	CY-09 ameliorates high-fat diet-induced hepatic steatosis	[304]
		Osteoarthritis	CY-09 attenuates osteoarthritis development through inhibiting NLRP3-mediated pyroptosis of chondrocytes	[305]
	MNS	Pancreatic cancer	MNS inhibits cell invasion, migration, and proliferation. Combination of MNS with cytokine-induced killer cells decreases tumor growth	[306]
		Breast cancer	MNS suppresses metastasis properties of cells	[307]
		Burn wound	MNS ameliorates burn wound progression, neutrophil infiltration, and cytokine production by inhibiting NLRP3	[308]
	Oridonin	Peritonitis, gouty arthritis, and type 2 diabetes	Oridonin shows preventive and therapeutic efficacy in three mouse models of NLRP3-related diseases	[255]
		Small cell lung cancer	Oridonin attenuates migration and EMT of cancer cells	[309]
		Oral cancer	Oridonin impedes cell growth	[310]
	Glyburide	Lung cancer	Glyburide attenuates inflammation-related lung tumorigenesis by inhibiting NLRP3	[311]
	BOT-4-one	Urate-induced peritonitis	BOT-4-one shows strong protective effect against urate-induced peritonitis through inhibiting NLRP3	[312]
	BOT-4-one	Lymphoma	BOT-4-one suppresses proliferation and survival of lymphoma cells	[313]
	Parthenolide	In vitro research	Parthenolide inhibits the activation of NLRP3	[256]
	Glycyrrhizin	In vitro research	Glycyrrhizin inhibits the activation of TLR4, NF-κB, and NLRP3	[256]
	NU9056	In vitro research	NU9056 inhibits NLRP3 activation indirectly through inhibiting KAT5	[79]
	Methylene blue	Spinal cord injury	Methylene blue alleviates neuroinflammation through inhibiting NLRP3	[314]
	Methylene blue	In vitro research	Methylene blue is a broad-spectrum inflammasome inhibitor against NLRP3, NLRC4, AIM2, and non-canonical inflammasomes	[261]
	Pioglitazone	Traumatic brain injury	Pioglitazone treatment decreases expression of IL-1β, caspase-1, and NLRP3	[315]
	Fenamate NSAIDs	Alzheimer’s disease	Fenamate NSAIDs show therapeutic effects in Alzheimer’s disease through inhibiting NLRP3	[316]
	Resveratrol	Renal cancer	Resveratrol suppresses tumor progression through downregulating expression of NLRP3	[258]
		Doxorubicin-induced cardiotoxicity	Resveratrol reduces doxorubicin-induced cardiac injury and systemic inflammation	[259]
		Radiation-induced inflammatory bowel disease	Resveratrol alleviates bowel inflammation after irradiation by repressing NLRP3 expression	[228]
	JC-171	Multiple sclerosis	JC-171 delays progression of multiple sclerosis by interfering with NLRP3/ASC interaction	[317]
	JC-124	Alzheimer’s disease	JC-124 inhibits NLRP3 and shows neuroprotective effect	[318]
	Colchicine	Ischemia–reperfusion injury	Colchicine reduces liver damage in mouse model of renal ischemia–reperfusion injury by downregulating NLRP3, caspase-1, and IL-1β	[319]
	IFN39	In vitro research	IFN39 inhibits NLRP3-ASC speckle formation through blocking NEK7-NLRP3 interaction	[320]
	Maxing shigan decoction	Mycoplasma pneumonia infection	Maxing shigan decoction suppresses NLRP3-induced cell pyroptosis and IL-1β production after Mycoplasma pneumonia infection	[321]
	Sulforaphane	In vitro research	Sulforaphane attenuates activation of both NLRP3 and NLRC4	[262]
	Sulforaphane	Ischemia–reperfusion injury	Sulforaphane reduces retinal ischemia–reperfusion injury and reduces retinal ganglion cell death	[322]
	β-hydroxybutyrate	Glioma	NLRP3-mediated migration of glioma cells is suppressed by β-hydroxybutyrate	[323]
		Alzheimer’s disease	Pathology of Alzheimer’s disease is alleviated by β-hydroxybutyrate through inhibiting NLRP3	[324]
		Gout flares	Gout flares is relieved by β-hydroxybutyrate through inhibiting NLRP3 in neutrophil	[325]
	16,673-34-0	Cardiac dysfunction	Western diet-induced cardiac dysfunction is prevented by 16,673-34-0	[326]
	16,673-34-0	Ischemia–reperfusion injury	Heart ischemia–reperfusion injury is reduced by 16,673-34-0	[327]
	Celastrol	Melanoma	Celastrol inhibits migration and invasion of melanoma cells by suppressing macrophage-derived NLRP3/IL-1β pathway	[172]
	NBC series	In vitro research	NBC series inhibits activation of NLRP3 without affecting Ca²⁺ homeostasis	[328]
	Apigenin	Peritonitis	Apigenin ameliorates inflammatory symptoms related to NLRP3 activation	[329]
	Fc11a-2	Colitis	Fc11a-2 attenuates symptoms and secretion of pro-inflammatory cytokines in colitis by targeting NLRP3	[330]
	Formononetin	Colitis	Formononetin prevents colonic cell injury by reducing NLRP3, ASC, and IL-1β protein levels	[331]
	Triptolide	Myocardial remodeling	Triptolide attenuates myocardial remodeling by targeting NLRP3	[332]
	Andrographolide	Colitis-associated cancer	Andrographolide reduces colitis and tumor burden by inhibiting NLRP3 and triggering mitophagy	[333]
	Curcumin	Colitis	Curcumin ameliorates colitis symptoms by inhibiting NLRP3 in macrophages	[334]
	Quinazolin-4(3H)-ones	In vitro research	Quinazolin-4(3H)-ones inhibits NLRP3-mediated IL-1β release in monocyte	[335]
	Arglabin	Atherosclerosis	Arglabin shows anti-atherogenic effects partially through targeting NLRP3	[336]
	LFG-500	NSCLS	LFG-500 suppresses NLRP3-mediated EMT, migration, and metastasis	[178]
	ibrutinib	In vitro research	Ibrutinib indirectly inhibits NLRP3 inflammasomes by suppressing phosphorylated BTK that directly inhibited NLRP3 and ASC	[257]
AIM2 inhibitor	Andrographolide	Radiation-induced lung inflammation	Andrographolide prevents AIM2 from entering the nucleus	[224]
	glycyrrhizin	In vitro research	Glycyrrhizin inhibits activation of AIM2	[256]
	Methylene blue	In vitro research	Methylene blue is a broad-spectrum inflammasome inhibitor against NLRP3, NLRC4, AIM2, and non-canonical inflammasomes	[261]
NLRC4 inhibitor	Sulforaphane	In vitro research	Sulforaphane attenuates activation of both NLRP3 and NLRC4	[262]
NLRC4 inhibitor	Methylene blue	In vitro research	Methylene blue is a broad-spectrum inflammasome inhibitor against NLRP3, NLRC4, AIM2, and non-canonical inflammasomes	[261]
ASC inhibitor	CRID3 (MCC950)	In vitro research	CRID3 directly interacts with ASC causing blocked formation of ASC specks	[271]
	CRID3 (MCC950)	Spinal cord injury	CRID3 improves histology and behavior results after spinal cord injury by inhibiting ASC-related inflammasomes	[270]
	ibrutinib	In vitro research	Ibrutinib indirectly inhibits NLRP3 inflammasomes by suppressing phosphorylated BTK that directly inhibits NLRP3 and ASC	[257]
Caspase-1 inhibitor	VX-765	NSCLC	ROS/NF-κB/NLRP3/GSDMD axis-induced pyroptosis is inhibited by VX-765	[263]
		NSCLC	VX-765 inhibits cell migration by blocking AIM2 signal	[264]
		Alzheimer’s disease	VX-765 alleviates neuropathology and cognitive impairment in mouse model of Alzheimer’s disease	[337]
	VX-740	Colitis	VX-740 mitigates IL-1β secretion in dextran sodium sulfate-induced colitis	[338]
	VX-740	Osteoarthritis	VX-740 attenuates joint damage in mouse models of osteoarthritis	[339]
	VRT-018858	Transient ischemia	VRT-018858 shows protective effect against brain damage in transient ischemia	[340]
	Thalidomide	Melanoma	Thalidomide reduces tumor growth through inhibiting caspase-1 in MDSCs	[267]
	Ac-YVAD-CHO	Melanoma	Ac-YVAD-CHO inhibits iNOS-induced apoptosis	[268]
	Ac-YVAD-CHO	Melanoma	Ac-YVAD-CHO inhibits phloretin-induced apoptosis	[269]
	Ac-FLTD-CMK	Traumatic brain injury	Ac-FLTD-CMK shows neuroprotective effect in traumatic brain injury through inhibiting pyroptosis	[341]
	Ac-YVAD-CMK	Hepatocellular carcinoma	Ac-YVAD-CMK reverses caspase-1-mediated pyroptosis	[265]
		Breast cancer	Ac-YVAD-CMK increases proliferation and invasion, while decreasing apoptosis in cancer cells	[342]
		Renal cancer	Ac-YVAD-CMK abrogates AIM2-mediated anti-tumor effect	[343]
	Z-YVAD-fmk	Prostate cancer	Z-YVAD-fmk inhibits radiation-induced apoptosis by targeting caspase-1	[266]
	Q-VD-OPh	Leukemia	Q-VD-OPh in combination with vitamin D show anti-leukemia effects through inducing differentiation	[344]
IL-1α inhibitor	Lutikizumab	In vitro research	Lutikizumab specifically binds to IL-1α and IL-1β simultaneously	[345]
IL-1β inhibitor	Canakinumab	rheumatoid arthritis	Canakinumab is effective in joint inflammation models	[278]
	Rilonacept	autoimmune disorders	High-affinity “cytokine traps” potently block cytokines in vitro and in vivo	[279, 280]
	Gevokizumab	Heart failure	Gevokizumab limits cardiac remodeling and coronary dysfunction	[281]
	Lutikizumab	In vitro research	Lutikizumab specifically binds to IL-1α and IL-1β simultaneously	[345]
IL-18 inhibitor	IL-18BP	Colorectal carcinoma	IL-18BP binds to IL-18 with high-affinity limiting anti-tumor immunity	[282]
IL-1R inhibitor	Anakinra	Burkitt lymphoma	Anakinra abrogates cytokine release syndrome during CAR-T therapy	[289]
		Breast cancer	Anakinra reduces tumor growth by abrogating IL-22 production	[283]
		Mesothelioma	Synergistic effect is observed in combined of cisplatin and Anakinra against malignant mesothelioma	[215]
	AMG 108	Osteoarthritis	AMG 108 decreases neutrophil count	[346]
GSDMD inhibitor	Necrosulfonamide	NSCLC	ROS/NF-κB/NLRP3/GSDMD axis-induced pyroptosis is inhibited by necrosulfonamide	[263]
	Necrosulfonamide	Alzheimer’s disease	Necrosulfonamide inhibits β-amyloid-induced neuronal pyroptosis	[347]
	LDC7559	In vitro research	LDC7559 binds to GSDMD and inhibits NETosis	[272]
	Disulfiram	Breast cancer	Metabolite of disulfiram shows anticancer effect	[348]
		Nasopharyngeal cancer	Disulfiram/copper shows potent cytotoxic effects on cancer cells and fibroblasts	[275]
		Sepsis	Disulfiram prevents NET release from neutrophils leading to reduced multiple organ dysfunction	[273]
		In vitro research	Disulfiram inhibits GSDMD pore formation	[274]
	Bay 11–7082	Multiple myeloma	Bay 11–7082 induces apoptosis in multiple myeloma cells	[276, 277]
	Bay 11–7082	In vitro research	Bay 11–7082 inhibits GSDMD pore formation	[274]
NLRP3 activator	Polyphyllin VI	NSCLC	Polyphyllin VI induces pyroptosis through activating NLRP3	[263]
	17β-estradiol	Hepatocellular carcinoma	17β-estradiol provokes pyroptosis via NLRP3	[265, 290]
	BMS-986299	Cancer	BMS-986299 shows potential anticancer effects	[3]

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