RESUMO
Benzo[a]pyrene (B[a]P) exposure has been associated with the alteration in epigenetic marks that are involved in cancer development. Biotinidase (BTD) and holocarboxylase synthetase (HCS) are 2 major enzymes involved in maintaining the homeostasis of biotinylation, and the deregulation of this pathway has been associated with a number of cancers. However, the link between B[a]P exposure and the dysregulation of BTD/HCS in B[a]P-associated tumorigenesis is unknown. Here we showed that the expression of both BTD and HCS was significantly decreased upon B[a]P treatment in human bronchial epithelial (16HBE) cells. Benzo[a]pyrene exposure led to the global loss of DNA methylation by immunofluorescence, which coincided with the reduction in acetylation levels on histones H3 and H4 in 16HBE cells. Consistent with decreased histone acetylation, histone deacetylases (HDACs) HDAC2 and HDAC3 were significantly upregulated in a dosage-dependent manner. When DNA methylation or HDAC activity was inhibited, we found that the reduction in BTD and HCS was separately regulated through distinct epigenetic mechanisms. Together, our results suggested the potential link between B[a]P toxicity and deregulation of biotin homeostasis pathway in B[a]P-associated cancer development.
Assuntos
Benzo(a)pireno/toxicidade , Biotina/metabolismo , Carcinógenos/toxicidade , Células Epiteliais/efeitos dos fármacos , Acetilação/efeitos dos fármacos , Biotinidase/metabolismo , Brônquios/citologia , Carbono-Nitrogênio Ligases/metabolismo , Linhagem Celular , Metilação de DNA , Epigênese Genética , Células Epiteliais/metabolismo , Histona Desacetilase 2/metabolismo , Histona Desacetilases/metabolismo , Histonas/efeitos dos fármacos , Histonas/metabolismo , HumanosRESUMO
Pantoea dispersa is a Gram-negative bacterium that exists in a variety of environments and has potential in many commercial and agricultural applications, such as biotechnology, environmental protection, soil bioremediation, and plant growth stimulation. However, P. dispersa is also a harmful pathogen to both humans and plants. This "double-edged sword" phenomenon is not uncommon in nature. To ensure survival, microorganisms respond to both environmental and biological stimuli, which could be beneficial or detrimental to other species. Therefore, to harness the full potential of P. dispersa, while minimizing potential harm, it is imperative to unravel its genetic makeup, understand its ecological interactions and underlying mechanisms. This review aims to provide a comprehensive and up-to-date overview of the genetic and biological characteristics of P. dispersa, in addition to potential impacts on plants and humans, as well as to provide insights into potential applications.
Assuntos
Pantoea , Humanos , Biodegradação Ambiental , Pantoea/fisiologia , Solo , Agricultura , PlantasRESUMO
Ganoderma lucidum polysaccharides (GLPs), which were purified from the medicinal herb G. lucidum followed by ethanol precipitation, protein depletion using the Sevage assay, purification using DEAEcellulose (DE-52), dialysis and the use of ultrafiltration membranes, are used as an ingredient in traditional anticancer treatments in China. The aim of the current study was to evaluate the anticancer effects and investigate the underlying molecular mechanisms of GLPs on LoVo human colon cancer cells. The results demonstrated that the GLPmediated anticancer effect in LoVo cells was characterized by cytotoxicity, migration inhibition, enhanced DNA fragmentation, morphological alterations and increased lactate dehydrogenase release. Furthermore, the activation of caspases3, 8 and 9 was involved in GLPstimulated apoptosis. Additionally, treatment with GLPs promoted the expression of Fas and caspase3 proteins, whilst reducing the expression of cleaved poly(ADPribose) polymerase. These data indicate that GLPs demonstrate potential antitumor activity in human colon cancer cells, predominantly through the inhibition of migration and induction of apoptosis. Furthermore, activation of the Fas/caspase-dependent apoptosis pathway is involved in the cytotoxicity of GLPs.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Polissacarídeos/farmacologia , Reishi/química , Antineoplásicos Fitogênicos/química , Caspase 3/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Medicamentos de Ervas Chinesas/química , Ativação Enzimática/efeitos dos fármacos , Humanos , Poli(ADP-Ribose) Polimerases/metabolismo , Polissacarídeos/químicaRESUMO
5,8-Quinazolinediones modified at positions 6 and 7 were synthesized and tested for in vitro antifungal activities against Candida species and Aspergillus niger. Most of 5,8-quinazolinediones 3-5 generally exhibited potent antifungal activity. 6-Arylamino-7-chloro-5,8-quinazolinediones (3) generally showed more potent antifungal activity than 7-arylthio-5,8-quinzolinediones (4) and 6,7-bis-(arylthio)-5,8-quinazolinediones (5).
Assuntos
Antifúngicos/síntese química , Antifúngicos/farmacologia , Quinazolinas/síntese química , Quinazolinas/farmacologia , Aspergillus niger/efeitos dos fármacos , Candida/efeitos dos fármacos , Cromatografia em Camada Fina , Fungos/efeitos dos fármacos , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Espectrometria de Massas por Ionização por Electrospray , Relação Estrutura-AtividadeRESUMO
Ganoderma lucidum polysaccharides (GLP) extracted from Ganoderma lucidum have been shown to induce cell death in some kinds of cancer cells. This study investigated the cytotoxic and apoptotic effect of GLP on HCT-116 human colon cancer cells and the molecular mechanisms involved. Cell proliferation, cell migration, lactate dehydrogenase (LDH) levels and intracellular free calcium levels ([Ca(2+)]i) were determined by MTT, wound-healing, LDH release and fluorescence assays, respectively. Cell apoptosis was observed by scanning and transmission electron microscopy. For the mechanism studies, caspase-8 activation, and Fas and caspase-3 expression were evaluated. Treatment of HCT-116 cells with various concentrations of GLP (0.625-5 mg/mL) resulted in a significant decrease in cell viability (P< 0.01). This study showed that the antitumor activity of GLP was related to cell migration inhibition, cell morphology changes, intracellular Ca(2+) elevation and LDH release. Also, increase in the levels of caspase-8 activity was involved in GLP-induced apoptosis. Western blotting indicated that Fas and caspase-3 protein expression was up-regulated after exposure to GLP. This investigation demonstrated for the first time that GLP shows prominent anticancer activities against the HCT-116 human colon cancer cell line through triggering intracellular calcium release and the death receptor pathway.
Assuntos
Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Neoplasias do Colo/tratamento farmacológico , Proteína de Domínio de Morte Associada a Fas/metabolismo , Polissacarídeos Fúngicos/farmacologia , Cálcio/análise , Caspase 8/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Polissacarídeos Fúngicos/efeitos adversos , Células HCT116 , Humanos , L-Lactato Desidrogenase/biossíntese , Masculino , Microscopia Eletrônica de Transmissão , Reishi , Transdução de Sinais/efeitos dos fármacosRESUMO
In this paper, an endophytic strain B-001 against tobacco bacterial wilt (Ralstonia solanacarum) was isolated from the stem of healthy tobacco in R. solanacarum-infected fields, which had a stronger inhibitory effect on some kinds of gram-positive bacteria, gram-negative bacteria, and pathogenic fungi. This strain belonged to Bacillus, and its 16S rDNA after PCR and sequencing had an accession of GenBank being DQ444283. The 16S rDNA phylogenetic tree was constructed with MEGA3, and compared with the published 16S rDNA sequences of relative bacteria species. B-001 had a 99.2% sequence similarity with Bacillus subtilis (DQ415893). According to the morphological, physiological and biochemical characteristics, and based on phylogenetic analysis, B-001 was identified as a strain of B. subtilis. Field experiments in Guiyang and Ningxiang counties of Hunan Province showed that in 2005 and 2006, the control efficacy of B-001 on R. solanacarum ranged from 40.03% to 78. 14%, better than that of Streptomycini.
Assuntos
Bacillus subtilis/isolamento & purificação , Nicotiana/microbiologia , Doenças das Plantas/microbiologia , Ralstonia solanacearum , Bacillus subtilis/fisiologia , Controle Biológico de Vetores/métodos , Ralstonia solanacearum/genética , Ralstonia solanacearum/patogenicidade , Ralstonia solanacearum/fisiologiaRESUMO
A series of 6-arylamino-7-chloro-quinazoline-5,8-diones were prepared and evaluated for their in vitro cytotoxicity in cultured human cancer cell lines A549 (lung cancer), Col2 (colon cancer), and SNU-638 (stomach cancer). The preliminary structure-activity relationship has been described for providing further development of potent antitumor agents. To further investigate the cytotoxic mechanism, the effects of test compounds on DNA topoisomerase I and II activities have been assessed.