Small molecule-driven mitophagy-mediated NLRP3 inflammasome inhibition is responsible for the prevention of colitis-associated cancer

Guo, Wenjie; Sun, Yang; Li, Wen; Wu, Xingxin; Guo, Lu; Cai, Peifen; Wu, Xuefeng; Wu, Xudong; Shen, Yan; Shu, Yongqian; Gu, Yanhong; Xu, Qiang

doi:10.4161/auto.28374

Cited by 235 publications

(175 citation statements)

References 60 publications

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“…Autophagy is a protector in tumor initiation and a booster in tumor progression, meanwhile, autophagy involves in inflammatory diseases by restricting inflammation and necrosis [57][58][59]. Recently, some reports have shown that novel therapies ameliorate CAC by regulating autophagy in tumor and immune cells [60][61][62]. As a vital autophagy inhibitor, whether HCQ modulates CAC through the autophagy pathway is unknown in this study.…”

Section: Discussionmentioning

confidence: 82%

Therapeutic effect of hydroxychloroquine on colorectal carcinogenesis in experimental murine colitis

Yao

Xie

et al. 2016

Biochemical Pharmacology

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Section: Discussionmentioning

confidence: 82%

Therapeutic effect of hydroxychloroquine on colorectal carcinogenesis in experimental murine colitis

Yao

Xie

et al. 2016

Biochemical Pharmacology

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“…Furthermore, evidence indicates that dysfunction of mitophagy also promotes tumorigenesis and neoplastic progression (4,5,14). Guo et al reported that the induction of mitophagy in macrophages prevents the progression of colitis-associated cancer (22). Moreover, tumorigenesis and metastasis are also promoted by mitochondrial reactive oxygen species (ROS) (23).…”

Section: Biological Role Of Mitophagymentioning

confidence: 99%

Dual Role of Mitophagy in Cancer Drug Resistance

Yan

2018

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“…A. paniculata has long been used as herbal medicine for the prevention and treatment of upper respiratory tract infection in Asian countries and in Scandinavia (14). Andrographolide has been shown to possess various biological activities, including antiviral (15), anticancer (13,16), anti-inflammatory (17,18) and antioxidative (15,19,20) activities.…”

mentioning

confidence: 99%

Andrographolide Restores Steroid Sensitivity To Block Lipopolysaccharide/IFN-γ–Induced IL-27 and Airway Hyperresponsiveness in Mice

Liao

Tan

Wong

2016

The Journal of Immunology

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LPS and IFN-γ alone or in combination have been implicated in the development of steroid resistance. Combined LPS/IFN-γ strongly upregulates IL-27 production, which has been linked to steroid-resistant airway hyperresponsiveness (AHR). Andrographolide, a bioactive molecule isolated from the plant Andrographis paniculata, has demonstrated anti-inflammatory and antioxidant properties. The present study investigated whether andrographolide could restore steroid sensitivity to block LPS/IFN-γ–induced IL-27 production and AHR via its antioxidative property. The mouse macrophage cell line Raw 264.7, mouse primary lung monocytes/macrophages, and BALB/c mice were treated with LPS/IFN-γ, in the presence and absence of dexamethasone and/or andrographolide. Levels of IL-27 in vitro and in vivo were examined and mouse AHR was assessed. Dexamethasone alone failed to inhibit LPS/IFN-γ–induced IL-27 production and AHR in mice. Andrographolide significantly restored the suppressive effect of dexamethasone on LPS/IFN-γ–induced IL-27 mRNA and protein levels in the macrophage cell line and primary lung monocytes/macrophages, mouse bronchoalveolar lavage fluid and lung tissues, and AHR in mice. LPS/IFN-γ markedly reduced the nuclear level of histone deacetylase (HDAC)2, an essential epigenetic enzyme that mediates steroid anti-inflammatory action. LPS/IFN-γ also decreased total HDAC activity but increased the total histone acetyltransferase/HDAC activity ratio in mouse lungs. Andrographolide significantly restored nuclear HDAC2 protein levels and total HDAC activity, and it diminished the total histone acetyltransferase/HDAC activity ratio in mouse lungs exposed to LPS/IFN-γ, possibly via suppression of PI3K/Akt/HDAC2 phosphorylation, and upregulation of the antioxidant transcription factor NF erythroid-2–related factor 2 level and DNA binding activity. Our data suggest that andrographolide may have therapeutic value in resensitizing steroid action in respiratory disorders such as asthma.

show abstract

Small molecule-driven mitophagy-mediated NLRP3 inflammasome inhibition is responsible for the prevention of colitis-associated cancer

Abstract: (2014) Small molecule-driven mitophagy-mediated NLRP3 inflammasome inhibition is responsible for the prevention of colitisassociated cancer, Autophagy, 10:6,[972][973][974][975][976][977][978][979][980][981][982][983][984][985]

Cited by 235 publications

References 60 publications

Therapeutic effect of hydroxychloroquine on colorectal carcinogenesis in experimental murine colitis

Therapeutic effect of hydroxychloroquine on colorectal carcinogenesis in experimental murine colitis

Dual Role of Mitophagy in Cancer Drug Resistance

Andrographolide Restores Steroid Sensitivity To Block Lipopolysaccharide/IFN-γ–Induced IL-27 and Airway Hyperresponsiveness in Mice

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