The fungal secondary metabolite trichodimerol inhibits TGF-β dependent cellular effects and tube formation of MDA-MB-231 cells

Serwe, Annegret; Anke, Timm; Erkel, Gerhard

doi:10.1007/s10637-008-9201-9

Cited by 5 publications

(5 citation statements)

References 47 publications

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“…[26] In addition, Serwe et al reported that trichodimerol inhibited Janus kinase/Signal transducers and activators of transcription (Jak/STAT) and NFкB. [27] Our data are consistent with these results by showing that sorbicillinoids inhibited NO production of macrophage RAW264.7 cells through suppressing the expression of iNOS. Further, we demonstrate that these compounds inhibited the activation of the downstream factor NFкB.…”

Section: Resultssupporting

confidence: 89%

“…Mazzucco et al reported that trichodimerol inhibited LPS mediated tumor necrosis factor‐α (TNF‐α) secretion by inhibiting the synthesis of prostaglandin H synthase‐2 (PGHS‐2) enzyme at the transcription level [26] . In addition, Serwe et al reported that trichodimerol inhibited Janus kinase/Signal transducers and activators of transcription (Jak/STAT) and NFκB [27] . Our data are consistent with these results by showing that sorbicillinoids inhibited NO production of macrophage RAW264.7 cells through suppressing the expression of iNOS.…”

Section: Resultsmentioning

confidence: 99%

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Isolation and Characterization of Anti‐Inflammatory Sorbicillinoids from the Mangrove‐Derived Fungus Penicillium sp. DM815

Ding¹,

Wang²,

Li³

et al. 2021

Chemistry & Biodiversity

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Marine derived fungus has gained increasing ground in the discovery of novel lead compounds with potent biological activities including anti-inflammation. Here, we first report the characterization of one new sorbicillinoid (1) and fourteen known compounds (2 -15) from the ethyl acetate (AcOEt) extract of a cultured mangrove derived fungus Penicillium sp. DM815 by UV, IR, HR ESI-Q-TOF MS, and NMR spectra. We then evaluated the anti-inflammatory effects of eleven sorbicillinoids (1 -11) using cultured macrophage RAW264.7 cells. The results show that compound 9, and to a lesser degree compound 5, significantly inhibited the Gramnegative bacteria lipopolysaccharide (LPS)-induced upregulation of the inducible nitric oxide synthase (iNOS). Consistently, compounds 5 and 9 significantly reduced the level of nitric oxide (NO), the product of iNOS, induced by LPS. We further show that these two compounds dose-dependently inhibited LPS-triggered iNOS expression and NO production, but had no effect on proliferation of RAW264.7 cells in the presence of LPS. In conclusion, our study identifies novel and known sorbicillinoids as potent anti-inflammatory agents, holding the promise of developing novel anti-inflammation treatment in the future.

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Section: Resultssupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Isolation and Characterization of Anti‐Inflammatory Sorbicillinoids from the Mangrove‐Derived Fungus Penicillium sp. DM815

Ding¹,

Wang²,

Li³

et al. 2021

Chemistry & Biodiversity

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“…To complement our data on secondary metabolite production on complex media on sexual development and minimal media on liquid standing cultures or plates with glucose as carbon source, we used liquid shake flask cultures with cellulose as carbon source. We focused on the polyketide trichodimerol (Shirota et al ., ), a fungal metabolite with potential anticancer activity (Serwe et al ., ) and the peptaibol antibiotic paracelsin (Brückner et al ., ) as model substances. Both metabolites were previously shown to be produced in T. reesei (Brückner et al ., ; Monroy et al ., ).…”

Section: Resultsmentioning

confidence: 99%

SUB1 has photoreceptor dependent and independent functions in sexual development and secondary metabolism in Trichoderma reesei

Bazafkan

Beier

Stappler

et al. 2017

Molecular Microbiology

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Light dependent processes are involved in the regulation of growth, development and enzyme production in Trichoderma reesei. The photoreceptors BLR1, BLR2 and ENV1 exert crucial functions in these processes. We analyzed the involvement of the transcription factor SUB1 in sexual development as well as secondary metabolism and its position in the light signaling cascade. SUB1 influences growth and in contrast to its homologue in N. crassa, SUB1 is not essential for fruiting body formation and male fertility in T. reesei, but required for female fertility. Accordingly, SUB1 is involved in the regulation of the pheromone system of T. reesei. Female sterility of mutants lacking env1 is rescued in triple mutants of blr1, blr2 and env1, but not in double mutants of these genes. Confrontation of strains lacking sub1 results in growth arrest prior to contact of the potential mating partners. This effect is at least in part due to altered secondary metabolite production. Additionally, together with BLR1 and BLR2, SUB1 is essential for spore pigmentation and transcription of pks4, and secondary metabolism is regulated by SUB1 in a light- and nutrient dependent manner. Our results hence indicate rewiring of several pathways targeted by SUB1 in T. reesei.

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“…In recent years, it was demonstrated that trichodimerol produced by Trichoderma longibrachiatum has the ability to cause inhibition of tumor cell growth. Interestingly, gliotoxins and related compounds have recently attracted much interest as pro-apoptotic agents with potential immunomodulating properties that may be valuable in the management of advanced autoimmune diseases and disseminated cancers [51][52][53][54].…”

Section: Immunotoxins Of Fungal Originmentioning

confidence: 99%

Fungal Secondary Metabolites: A Promising Source of Antineoplastic Drugs

Ahmed¹,

Shikh²,

Ghoneimy³

et al. 2010

CCTR

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The rapid progress in understanding the molecular biology of cancer has made a large impact on the design and development of novel therapeutic strategies prompted by the multi-factorial limitations of the current chemotherapeutic modalities. Given that the development of newer antineoplastic drugs continues to rely heavily on isolation from natural sources rather than applications based on rational drug design and combinatorial chemistry, fungal secondary metabolites rank high on the list of potential targets for the discovery of novel chemotherapeutic agents. They represent a diverse group of bioactive compounds characterized by their origin and biosynthetic pathways. Also, they serve as regulators, chemical messengers in developmental processes, or as antibiotics. A broad variety of fungal secondary metabolites possess potent antitumor activity. Alpha sarcin, gliotoxins, trichodimerol, L-lysine alpha-oxidase, fumagillin, declauxin, chrysanthones, fungal-derived low molecular weight inhibitors of angiogenesis e.g. TNP-470, retamycin, daunorubicin, and doxorubicin all have been shown to exert potent antitumor activity. Inhibition of protein synthesis, induction of DNA breakage and apoptosis, as well as blockade of angiogenesis are examples of the multiple antitumor mechanisms of fungal secondary metabolites. The current review explores the potential use of fungal secondary metabolites as antineoplastic drugs with special reference to the novel hepatoma growth-inhibition factor that we recently characterized from Trichoderma viride.

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The fungal secondary metabolite trichodimerol inhibits TGF-β dependent cellular effects and tube formation of MDA-MB-231 cells

Cited by 5 publications

References 47 publications

Isolation and Characterization of Anti‐Inflammatory Sorbicillinoids from the Mangrove‐Derived Fungus Penicillium sp. DM815

Isolation and Characterization of Anti‐Inflammatory Sorbicillinoids from the Mangrove‐Derived Fungus Penicillium sp. DM815

SUB1 has photoreceptor dependent and independent functions in sexual development and secondary metabolism in Trichoderma reesei

Fungal Secondary Metabolites: A Promising Source of Antineoplastic Drugs

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