Fumigaclavine C inhibits tumor necrosis factor α production via suppression of toll-like receptor 4 and nuclear factor κB activation in macrophages

Du, Rong; Li, Erguang; Cao, Yin; Song, Yong; Tan, Ren Xiang

doi:10.1016/j.lfs.2011.06.015

Cited by 28 publications

(18 citation statements)

References 32 publications

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“…Hence, it may be expected that fumigaclavine C might have more or less similar cytotoxic effects on other cancer cell lines. Moreover, Du and colleagues revealed that the compound does not exert any detectable cytotoxicity on RAW 264.7 cells at concentrations up to 100 μM [21]. These findings indicate that fumigaclavine C shows a selective toxicity towards cells, which is an interesting characteristics in chemo preventive agents, as most potent cytotoxic compounds result in several side effects due to lack of selectivity.…”

Section: Discussionmentioning

confidence: 99%

Fumigaclavine C from a Marine-Derived Fungus Aspergillus Fumigatus Induces Apoptosis in MCF-7 Breast Cancer Cells

Himaya

Dewapriya

et al. 2013

Marine Drugs

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Recently, much attention has been given to discovering natural compounds as potent anti-cancer candidates. In the present study, the anti-cancer effects of fumigaclavine C, isolated from a marine-derived fungus, Aspergillus fumigatus, was evaluated in vitro. In order to investigate the impact of fumigaclavine C on inhibition of proliferation and induction of apoptosis in breast cancer, MCF-7 cells were treated with various concentrations of fumigaclavine C, and fumigaclavine C showed significant cytotoxicity towards MCF-7 cells. Anti-proliferation was analyzed via cell mobility and mitogen-activated protein kinase (MAPK) signaling pathway. In addition, fumigaclavine C showed potent inhibition on the protein and gene level expressions of MMP-2, -9 in MCF-7 cells which were manifested in Western blot and reverse transcription polymerase chain reaction (RT-PCR) results. The apoptosis induction abilities of the fumigaclvine C was studied by analyzing the expression of apoptosis related proteins, cell cycle analysis, DNA fragmentation and molecular docking studies. It was found that fumigaclavine C fragmented the MCF-7 cell DNA and arrested the cell cycle by modulating the apoptotic protein expressions. Moreover, fumigaclavine C significantly down-regulated the NF-kappa-B cell survival pathway. Collectively, data suggest that fumigaclavine C has a potential to be developed as a therapeutic candidate for breast cancer.

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Section: Discussionmentioning

confidence: 99%

Fumigaclavine C from a Marine-Derived Fungus Aspergillus Fumigatus Induces Apoptosis in MCF-7 Breast Cancer Cells

Himaya

Dewapriya

et al. 2013

Marine Drugs

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“…To study the effect of miR-181a on the LPS-induced activation of NF-κB, a NF-κB luciferase reporter gene assay was carried out as described previously ( Du et al, 2011 ). Briefly, macrophages were co-transfected with pNF-κB-Luc, pRL-TK control vectors and miR-181a mimics along with indicated controls.…”

Section: Methodsmentioning

confidence: 99%

Downregulation of TLR4 by miR-181a Provides Negative Feedback Regulation to Lipopolysaccharide-Induced Inflammation

et al. 2018

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Acute lung injury (ALI) is a progressive clinical disease with a high mortality rate, and characterized by an excessive uncontrolled inflammatory response. MicroRNAs (miRNAs) play a critical role in various human inflammatory diseases, and have been recognized as important regulators of inflammation. However, the regulatory mechanisms mediated by miRNAs involved in Lipopolysaccharide (LPS)-induced inflammation in ALI remain hazy. In this study, we found that miR-181a expression in the lung tissues of ALI mice and LPS-stimulated RAW 264.7 macrophages is dramatically reduced. We also show that over-expression of miR-181a significantly decreased the production of inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, whereas inhibition of miR-181a reversed this decrease. Moreover, miR-181a inhibits NF-κB activation and accumulation of reactive oxygen species (ROS) by targeting TLR4 expression. We further verify that miR-181a suppresses TLR4 expression by binding directly to the 3′-UTR of TLR4. Therefore, we provide the first evidence for the negative regulation of miR-181a in LPS-induced inflammation via the suppression of ROS generation and TLR4-NF-κB pathway.

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“…The biological activities of the novel alkaloids are unknown and will require further study. Based on their structures, however, it is possible that unknowns A and B will have activities similar to those of fumigaclavine C, which has anti-inflammatory activity (38). In summation, we have reprogrammed A. fumigatus to produce lysergic acid by heterologous expression of an isomerase allele of easA in a native easA knockout strain (to produce agroclavine substrate) concomitant with the expression of the P450 monooxygenase gene cloA.…”

Section: Fig 4 Qualitative Analysis Of Ergot Alkaloids From Transformmentioning

confidence: 99%

Heterologous Expression of Lysergic Acid and Novel Ergot Alkaloids in Aspergillus fumigatus

Robinson

Panaccione

2014

Appl Environ Microbiol

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Different lineages of fungi produce distinct classes of ergot alkaloids. Lysergic acid-derived ergot alkaloids produced by fungi in the Clavicipitaceae are particularly important in agriculture and medicine. The pathway to lysergic acid is partly elucidated, but the gene encoding the enzyme that oxidizes the intermediate agroclavine is unknown. We investigated two candidate agroclavine oxidase genes from the fungus Epichloë festucae var. lolii ؋ Epichloë typhina isolate Lp1 (henceforth referred to as Epichloë sp. Lp1), which produces lysergic acid-derived ergot alkaloids. Candidate genes easH and cloA were expressed in a mutant strain of the mold Aspergillus fumigatus, which typically produces a subclass of ergot alkaloids not derived from agroclavine or lysergic acid. Candidate genes were coexpressed with the Epichloë sp. Lp1 allele of easA, which encodes an enzyme that catalyzed the synthesis of agroclavine from an A. fumigatus intermediate; the agroclavine then served as the substrate for the candidate agroclavine oxidases. Strains expressing easA and cloA from Epichloë sp. Lp1 produced lysergic acid from agroclavine, a process requiring a cumulative six-electron oxidation and a double-bond isomerization. Strains that accumulated excess agroclavine (as a result of Epichloë sp. Lp1 easA expression in the absence of cloA) metabolized it into two novel ergot alkaloids for which provisional structures were proposed on the basis of mass spectra and precursor feeding studies. Our data indicate that CloA catalyzes multiple reactions to produce lysergic acid from agroclavine and that combining genes from different ergot alkaloid pathways provides an effective strategy to engineer important pathway molecules and novel ergot alkaloids.

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Fumigaclavine C inhibits tumor necrosis factor α production via suppression of toll-like receptor 4 and nuclear factor κB activation in macrophages

Cited by 28 publications

References 32 publications

Fumigaclavine C from a Marine-Derived Fungus Aspergillus Fumigatus Induces Apoptosis in MCF-7 Breast Cancer Cells

Fumigaclavine C from a Marine-Derived Fungus Aspergillus Fumigatus Induces Apoptosis in MCF-7 Breast Cancer Cells

Downregulation of TLR4 by miR-181a Provides Negative Feedback Regulation to Lipopolysaccharide-Induced Inflammation

Heterologous Expression of Lysergic Acid and Novel Ergot Alkaloids in Aspergillus fumigatus

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