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1.
J Asian Nat Prod Res ; 23(6): 570-583, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32603193

RESUMO

Ent-kaur-15-en-17-al-18-oic acid (LL-3) was demonstrated that it can inhibit LPS-induced nitric oxide (NO) production and macrophage migration, maintain homeostasis of oxidative stress, including increased mitochondrial membrane potential (MMP), decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and maintenance of superoxide dismutase (SOD) and glutathione (GSH) activities and inhibit oxidative stress-induced P38 and nuclear factor κB (NF-κB) pathways to decrease inducible nitric oxide synthase (iNOS), cyclooxygense-2 (COX-2), and tumour necrosis factor (TNF)-α mRNA expressions without marked cytotoxicity. These findings revealed that LL-3 could serve as a candidate lead compound for further studying anti-inflammatory therapies.[Formula: see text].


Assuntos
Anti-Inflamatórios/farmacologia , Diterpenos do Tipo Caurano/farmacologia , NF-kappa B , Transdução de Sinais , Animais , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Lipopolissacarídeos , Camundongos , Estrutura Molecular , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Proteínas Quinases p38 Ativadas por Mitógeno
2.
Mar Drugs ; 18(8)2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32824227

RESUMO

The high toxicity of actinomycin D (Act D) severely limits its use as a first-line chemotherapeutic agent in the clinic. Actinomycin V (Act V), an analog of Act D, exhibited strong anticancer activity in our previous studies. Here, we provide evidence that Act V has less hepatorenal toxicity than Act D in vitro and in vivo, associated with the reactive oxygen species (ROS) pathway. Compared to Act D, Act V exhibited considerably stronger sensitivity for cancer cells and less toxicity to human normal liver LO-2 and human embryonic kidney 293T cells using the MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay. Notably, Act V caused less damage to both the liver and kidney than Act D in vivo, indicated by organ to body weight ratios, as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum creatinine (Scr) levels. Further experiments showed that the ROS pathway is involved in Act V-induced hepatorenal toxicity. Act V generates ROS and accumulates malondialdehyde (MDA), reducing levels of superoxide dismutase (SOD) and glutathione (GSH) in LO-2 and 293T cells. These findings indicate that Act V induces less hepatorenal toxicity than Act D in vitro and in vivo and merits further development as a potential therapeutic agent for the treatment of cancer.


Assuntos
Antibióticos Antineoplásicos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Dactinomicina/análogos & derivados , Dactinomicina/toxicidade , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Rim/metabolismo , Rim/patologia , Nefropatias/metabolismo , Nefropatias/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos
3.
Mar Drugs ; 17(10)2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31601054

RESUMO

Actinomycin V, extracted and separated from marine-derived actinomycete Streptomyces sp., as the superior potential replacement of actinomycin D (which showed defect for its hepatotoxicity) has revealed an ideal effect in the suppression of migration and invasion in human breast cancer cells as referred to in our previous study. In this study, the involvement of p53 in the cell cycle arrest and pro-apoptotic action of actinomycin V was investigated in human non-small-cell lung carcinoma A549 cells. Results from the 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide assay showed that cytotoxic activity of actinomycin V on A549 cells (with wild-type p53) was stronger than the NCI-H1299 cells (p53-deficient). Actinomycin V upregulated both of the protein and mRNA expression levels of p53, p21Waf1/Cip1 and Bax in A549 cells. For this situation, actinomycin V decreased the M-phase related proteins (Cdc2, Cdc25A and Cyclin B1) expression, arrested cells in G2/M phase and subsequently triggered apoptosis by mediating the Bcl-2 family proteins' expression (Bax and Bcl-2). Furthermore, the effects of cell cycle arrest and apoptosis in A549 cells which were induced by actinomycin V could be reversed by the pifithrin-α, a specific inhibitor of p53 transcriptional activity. Collectively, our results suggest that actinomycin V causes up-regulation of p53 by which the growth of A549 cells is suppressed for cell cycle arrest and apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Dactinomicina/farmacologia , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Proteína Supressora de Tumor p53/metabolismo , Células A549 , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Mitose/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
4.
Molecules ; 24(20)2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31652659

RESUMO

Ivalin, a natural compound isolated from Carpesium divaricatum, showed excellent microtubule depolymerization activities among human hepatocellular carcinoma in our previous work. Here, we investigated its functions on mitochondria-mediated apoptosis in hepatocellular carcinoma SMMC-7721 cells. DAPI (4',6-diamidino-2-phenylindole) staining, annexin V-fluorexcein isothiocyanate (FITC) apoptosis detection, and western blotting were applied to explore the apoptotic effect of Ivalin. Next, the induction effect of Ivalin on the mitochondrial pathway was also confirmed via a series of phenomena including the damage of mitochondria membrane potential, mitochondria cytochrome c escape, cleaved caspase-3 induction, and the reactive oxygen species generation. In this connection, we understood that Ivalin induced apoptosis through the mitochondrial pathway and the overload of reactive oxygen species. Furthermore, we found that the activation of nuclear factor-κB (NF-κB) and subsequent p53 induction were associated with the apoptotic effect of Ivalin. These data confirmed that Ivalin might be a promising pro-apoptotic compound that can be utilized as a potential drug for clinical treatment.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Lactonas/farmacologia , Neoplasias Hepáticas/metabolismo , Mitocôndrias/efeitos dos fármacos , NF-kappa B/metabolismo , Sesquiterpenos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Asteraceae/química , Carcinoma Hepatocelular/tratamento farmacológico , Caspase 3/metabolismo , Linhagem Celular Tumoral , Citocromos c/metabolismo , Proteínas de Ligação a DNA/metabolismo , Humanos , Lactonas/química , Lactonas/metabolismo , Lactonas/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/química , Sesquiterpenos/metabolismo , Sesquiterpenos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos
5.
Medicine (Baltimore) ; 98(36): e17009, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490383

RESUMO

Erythrina corallodendron L., a kind of landscape tree, has long been used as a traditional medicine. In this study, the composition of essential oil extracted from the leaves was analysed by GC-MS (gas chromatograph-mass spectrometer), with linalool identified as the main compound. Its cytotoxicity against MDA-MB-231, MCF-7 and HMLE cells was examined by MTT and cloning assays. Transwell and wound-healing assays were used to examine the inhibition of migration and invasion. Western blot, qRT-PCR and immunofluorescence staining were used to measure the mRNA and protein expression of factors related to EMT (snail, slug, E-cadherin, N-cadherin and vimentin). The essential oil of Erythrina corallodendron leaves was found to inhibit the proliferation, migration and invasion of breast cancer cells in a dose-dependent manner. The findings of this study suggest that the essential oil of E. corallodendron leaves may merit further investigation as a potential clinical or adjuvant drug for treating breast cancer migration and invasion.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Fitogênicos/análise , Neoplasias da Mama/tratamento farmacológico , Erythrina/química , Óleos Voláteis/uso terapêutico , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Células MCF-7 , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/farmacologia , Fitoterapia , Folhas de Planta/química
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