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1.
Artigo em Inglês | MEDLINE | ID: mdl-33238849

RESUMO

BACKGROUND: Xanthones are a class of heterocyclic natural products, which are promising sources of anticancer leads. Phomoxanthone B(PXB)and Phomoxanthone A(PXA)are xanthone dimers. PXA is well studied as an anti-cancer agent, but PXB is not. In our study, PXB was isolated from the endophytic fungus Phomopsis sp. By254. OBJECTIVE: The purpose of this study was to identify the underlying anti-tumor mechanisms of PXB in breast cancer MCF7 cell line. METHODS: Apoptosis, cell cycle, proliferation, invasion and migration assays were used to assess the antitumor activity of PXB. RNA sequencing was used to analyze the effect of PXB treatment on gene expression in MCF7 cells. RESULTS: PXB showed cytotoxicity toward a variety of tumor cells, especially MCF7 cells. PXB inhibited the migration and invasion, arrested cell cycle at G2/M phase and induced apoptosis associated with caspase-3 activation in MCF7 cells. The detailed transcriptome analysis revealed that PXB affected several pathways related to tumorigenesis, metabolisms-, and oxidative phosphorylation in MCF7 cells. KEGG transcriptome analysis revealed that PXB upregulated pro-survival signal pathways such as MAPK, PI3K-AKT and STAT3 pathways. We found that PXB also significantly upregulated the expression of IL24, DDIT3 and XAF1, which may contribute to PXB-induced apoptosis. We further found that PXB may downregulate oxidative phosphorylation by decreasing the expression of electron transport chain genes, especially MT-ND1, which is a potential unfavorable prognostic marker for ER-positive breast cancer. CONCLUSION: PXB exerts strong cytotoxicity against human tumor cells and has a potential for ER-positive breast cancer treatment.

2.
ACS Omega ; 5(40): 25927-25935, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33073119

RESUMO

Phomoxanthone A and B (PXA and PXB) are xanthone dimers and isolated from the endophytic fungus Phomopsis sp. By254. The results demonstrated that PXB and PXA are noncompetitive inhibitors of SHP2 and PTP1B and competitive inhibitors of SHP1. Molecular docking studies showed that PXB and PXA interact with conserved domains of protein tyrosine phosphatases such as the ß5-ß6 loop, WPD loop, P loop, and Q loop. PXA and PXB could significantly inhibit the cell proliferation in MCF7 cells. Our results indicated that these two compounds do not efficiently inhibit PTP1B and SHP2 activity. RNA sequencing showed that PXA and PXB may inhibit SHP1 activity in MCF7 cells leading to the upregulation of inflammatory factors. In addition to PTP inhibition, PXA and PXB are multitarget compounds to inhibit the proliferation of tumor cells. In conclusion, both compounds show inhibition of cancer cells and a certain degree of inflammatory stimulation, which make them promising for tumor immunotherapy.

3.
Sci Rep ; 8(1): 1956, 2018 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-29386632

RESUMO

China is currently the only country that has commercialized genetically engineered tree species, and this has attracted worldwide attention. As a perennial tree species, transgenic poplar has a long growth cycle and needs to be tested for long-term ecological risks. The main purpose of this study was to explore the ecological safety of perennial transgenic poplars in arthropod community, physical and chemical properties of soil, gene flow, and soil microbial diversity. The study found transgenic poplars could effectively inhibit the number of pests. Moreover, transgenic poplar 741 did not affect the stability of the arthropod community. Studies on the microbial diversity of poplar showed that transgenic poplars did not affect the physical and chemical properties of the soil and the soil microbial community structure. Furthermore, the microbial community structure was obviously affected by location and season. The results showed that a 5-year-old transgenic 741 poplar did not pose an ecological risk, and did not affect the microbial community structure or functional diversity. This study provides a reference for the ecological security evaluation of transgenic poplars, and provides a theoretical basis for promoting the commercialization of transgenic poplars.


Assuntos
Artrópodes/fisiologia , Bacillus thuringiensis/fisiologia , Biodiversidade , Populus/genética , Populus/parasitologia , Microbiologia do Solo , Animais , Análise Discriminante , Fluxo Gênico , Plantas Geneticamente Modificadas , Análise de Componente Principal , RNA Ribossômico 16S/genética , Solo/química , Especificidade da Espécie , Transgenes
4.
Eur J Pharmacol ; 795: 124-133, 2017 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-27939989

RESUMO

Shp2 is a classical non-receptor protein tyrosine phosphatase (PTP) involved in many human diseases such as Noonan syndrome and tumors, and identified as a potential therapeutic target. In order to find a potent and selective Shp2 inhibitor, we screened a diverse collection of the secondary metabolites from endophyte fungi using an in vitro enzyme assay, and finally identified a potent Shp2 inhibitor, HLP46 (demethylincisterol A3) from Pestalotiopsis sp. HLP46 was reported to have anti-tumor and anti-inflammation activity previously. We provide the first evidence that HLP46 is an inhibitor of the Shp2. HLP46 shows high selective inhibition of Shp2 over Shp1, PTP1B, Lyp, STEP, PTPRA and Cdc25b. Enzymatic kinetic analyses showed that HLP46 is a non-competitive inhibitor of Shp2. HLP46 interrupts Gab1-Shp2 association and blocked Shp2-dependent activation of the Ras/ERK signal pathway induced by EGF. Furthermore, HLP46 decreased Src activation and inhibit tumor cell migration and invasion. As expected, HLP46 has no effect on the Shp2-independent activation of ERK induced by PMA or on the activation of the PI3K/Akt pathway. We testified therapeutic efficacy targeting both Shp2 and PI3K in MCF7 cells. HLP46 does not show any synergistic inhibition with PI3K inhibitor in suppressing cell growth. Collectively, these results suggest that HLP46 is a selective Shp2 inhibitor and could inhibit Shp2-dependent cell signaling in human cells.


Assuntos
Inibidores Enzimáticos/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 11/antagonistas & inibidores , Esteróis/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/metabolismo , Fator de Crescimento Epidérmico/farmacologia , Células HEK293 , Humanos , Células MCF-7 , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Simulação de Acoplamento Molecular , Invasividade Neoplásica , Conformação Proteica , Proteína Tirosina Fosfatase não Receptora Tipo 11/química , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Esteróis/metabolismo , Xylariales/química , Proteínas ras/metabolismo
5.
Int J Syst Evol Microbiol ; 58(Pt 7): 1542-6, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18599691

RESUMO

A strain (HBUM 20028(T)) isolated from alkali lake soil in China was studied by a polyphasic taxonomic approach. The strain produced abundant aerial and substrate mycelia. Long spore chains were borne on the aerial mycelium, and the substrate mycelium was often arranged in a shape like a fence or palisade. The special characteristic of strain HBUM 20028(T) was its abundant growth under alkaline conditions, at pH 8.0-14.0. The cell wall of strain HBUM 20028(T) contained meso-diaminopimelic acid but no diagnostic sugar. Major phospholipids included diphosphatidylglycerol and phosphatidylcholine. The major menaquinones were MK-10(H(2)), MK-10(H(4)) and MK-10(H(6)). The major cellular fatty acids were iso-C(16 : 0) (31.66 %), anteiso-C(17 : 0) (14.85 %) and C(18 : 1)omega9c (14.73 %). All of these characters consistently indicated that strain HBUM 20028(T) belongs to the genus Nocardiopsis. DNA-DNA hybridization between the strain and type strains of related species gave relatedness values far below 70 %. Based on 16S rRNA gene sequence analysis, DNA relatedness and phenotypic characteristics, a novel species with the name Nocardiopsis valliformis sp. nov. is proposed. The type strain is HBUM 20028(T) (=DSM 45023(T) =CGMCC 4.2135(T)).


Assuntos
Actinomycetales/classificação , Actinomycetales/isolamento & purificação , Álcalis , Água Doce , Microbiologia do Solo , Actinomycetales/genética , Actinomycetales/ultraestrutura , China , Microscopia Eletrônica de Varredura , Dados de Sequência Molecular , Filogenia , RNA Ribossômico 16S/genética , Especificidade da Espécie
6.
Int J Syst Evol Microbiol ; 58(Pt 1): 195-9, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18175709

RESUMO

An actinomycete, strain HBUM 20038(T), was isolated from soil from Ganjiahu Natural Reserve in Xinjiang Province, in north-western China, and then characterized using a polyphasic approach. 16S rRNA gene sequence analysis confirmed that strain HBUM 20038(T) was a member of the genus Nocardiopsis, and the morphological and chemotaxonomic characteristics of the strain were also consistent with those of species of Nocardiopsis. DNA-DNA hybridization between the strain and related type strains gave relatedness values far below 70%. These results, together with physiological characteristics, showed that strain HBUM 20038(T) represents a novel species within the genus Nocardiopsis, for which the name Nocardiopsis ganjiahuensis sp. nov. is proposed. The type strain is HBUM 20038(T) (=DSM 45031(T) =CGMCC 4.3500(T)).


Assuntos
Actinomycetales/classificação , Actinomycetales/isolamento & purificação , Microbiologia do Solo , Actinomycetales/genética , Actinomycetales/fisiologia , Técnicas de Tipagem Bacteriana , China , DNA Bacteriano/análise , Ácidos Graxos/análise , Genes de RNAr , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Fenótipo , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Especificidade da Espécie
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