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1.
Eur J Pharmacol ; 868: 172881, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31866405

RESUMO

Psoriasis is a chronic, inflammatory skin disease with high incidence and high rates of relapse, for which no satisfactory treatments are currently available. Yes-associated protein (YAP) is highly expressed in psoriasis and may regulate the proliferation and apoptosis of keratinocytes. Danshen is a traditional Chinese medicine, commonly used in the treatment of psoriasis. Danshensu is the most abundant water-soluble component of Danshen, but its therapeutic mechanism is still unclear. In this study, MTT was used to detect the effects of different danshensu concentrations (0.125, 0.25, 0.5 mmol/l) on the proliferation of an M5-based psoriasis cell model. The effects of danshensu on cell cycle and apoptosis were detected by flow cytometry. Cyclins and apoptosis-related proteins were evaluated by Western blot. Danshensu (20, 40, 80 mg/kg/day) was administered intraperitoneally to the imiquimod (IMQ) psoriasis mouse model. After 7 days, the expression of YAP in the lesions was detected by immunohistochemistry and Western blot. We found that danshensu reduced the expression of YAP in the M5 psoriasis cell model, inhibited cell proliferation, induced cell cycle arrest in G0/G1 phase, and promoted cell apoptosis. All these effects were partly reverted by YAP overexpression. The skin lesions of IMQ mice were thinned and the scales reduced after intragastric administration of danshensu, which also resulted in dose-dependent inhibition of YAP expression. We concluded that danshensu prevents abnormal epidermis proliferation in psoriasis possibly by modulating YAP expression. Our work can provide a theoretical basis for the clinical application of Danshen in the treatment of psoriasis.

2.
Mol Med Rep ; 20(5): 4645-4653, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31545496

RESUMO

Previous studies have demonstrated that microRNA (miR)­146a is involved in the inflammatory response of atopic dermatitis (AD). The aim of the present study was to investigate the expression of miR­146a in the serum of patients with AD and in skin lesions of AD animal models. In addition, we aimed to predict and verify the target genes of miR­146a. miR­146a expression was measured in AD patient serum via reverse transcription­quantitative PCR. T­helper (Th)1 [CD4+; interferon (IFN)­Î³+] and Th2 [CD4+; interleukin (IL)­4+] expression in peripheral blood mononuclear cells was evaluated using flow cytometry. Following the establishment of a 2,4­dinitrofluorobenzene­induced C57BL/6 mouse AD model, Th1 (CD4+IFN­Î³+) and Th2 (CD4+IL­4+) expression was analyzed in murine spleen cells via flow cytometry. Plasmids were transfected into 293T cells and at 48 h post­transfection, cells were analyzed using a luciferase assay system. The results revealed that the AD group had a significantly lower Th1/Th2 ratio and a significantly higher miR­146a expression compared with the control group (P<0.05). Furthermore, a decreased Th1/Th2 ratio and a significantly increased miR­146a expression were observed in the model group compared with the control group (P<0.01). We also conducted a dual­luciferase assay to determine whether small ubiquitin­related modifier 1 (SUMO1) if the target gene of miR­146a. We observed a ~30% decrease in the relative luciferase activity in cells containing the 3'­untranslated region of SUMO1 + miR­146a). The results of the luciferase assay indicated that may be a direct mRNA target of miR­146a; however, the quantification of band density of SUMO1 expression following western blotting did not significantly differ. The development of animal models in AD research is of vital importance. The results revealed that miR­146a may be a potential regulator involved in the pathogenesis of AD. Furthermore, the current study determined that miR­146a could be a valuable marker of AD and thus, may be applied in the development of therapeutic strategies for treating AD.

3.
Iran J Allergy Asthma Immunol ; 18(4): 347-357, 2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31522443

RESUMO

Atopic dermatitis (AD) is a chronic, recurrent skin condition resulting from both genetic and environmental factors. In recent decades, the prevalence of AD has increased considerably in some countries. However, given that the role of genetics is unlikely to have changed over this short period, the increased prevalence is more likely to be explained by changes in environmental and maternal factors. The aim of this review is to comprehensively summarize the various factors impacting AD incidence in offspring and provide guidance for primary prevention. Recent research has demonstrated that environmental and climate factors, maternal history of allergies, gestational diabetes, and stress play essential roles in increasing the risk of AD in infants. Some factors have protective effects against the incidence of AD, including probiotic supplementation, fish intake, and moisturizers. This review also considers fundamental research into AD prevalence and factors that in the past were mistakenly thought to affect that prevalence, such as caesarean section and antigen avoidance. The potential influence of these factors on infant AD incidence remains inconclusive and needs further study. Furthermore, infants with a family history of atopic disease may benefit from early weaning or reduced breastfeeding duration.

4.
Biomed Res Int ; 2019: 7465272, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31355279

RESUMO

In parallel with the prevalence metabolic syndrome, nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in most countries. It features a constellation of simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and even hepatocellular carcinoma. There are no approved drugs for effective management of NAFLD and NASH. Jianpi Huoxue formula (JPHX) mainly consists of Atractylodes macrocephal (Baizhu), Salvia miltiorrhiza (Danshen), Rasux Paeonia Alba (Baishao), Rhizoma Alismatis (Zexie), and Fructus Schisandrae Chinensis (Wuweizi), which may have beneficial effects on NAFLD. The aim of the study was to identify the effect of JPHX on NAFLD. A NAFLD model was induced by methionine-choline-deficient food (MCD) in Wistar rats and orally administered with simultaneous JPHX, once a day for 8 weeks. Hepatocellular injury, lipid profile, inflammation, fibrosis, and apoptosis were evaluated. The results showed that JPHX significantly decreased the abnormal serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared with the MCD model (P<0.05). Furthermore, JPHX protected MCD diet-fed rats from accumulation of hepatic triglycerides (TG) and total cholesterol (TC). Histological examination demonstrated that JPHX noticeably normalized the NAFLD activity score (NAS). Moreover, JPHX ameliorated liver inflammation by decreasing TNF-α levels and reduced collagen and matrix metalloproteinases in MCD diet-fed rats. In addition, JPHX prevented rats from MCD-induced cellular apoptosis, as suggested by TUNEL staining, and suppressed the activation of caspase 3 and 7 proteins. JPHX also inhibited the phosphorylation of JNK. In conclusion, JPHX exhibited a hepatoprotective effect against NAFLD in an MCD experimental model.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Alimentos Formulados/efeitos adversos , Fígado , Hepatopatia Gordurosa não Alcoólica , Animais , Colina , Fígado/metabolismo , Fígado/patologia , Masculino , Metionina , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Ratos , Ratos Wistar
5.
BMC Infect Dis ; 19(1): 506, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182059

RESUMO

BACKGROUND: Scalp mycosis is often caused by dermatophytes and was so called tinea capitis. There is no published report caused by Aspergillus protuberus. We report a rare case of kerion-type scalp mycosis caused by A. protuberus. CASE PRESENTATION: A 5-year-old girl developed pyogenic mass with pain for 8 days and got a fever for 2 days prior to admission. Surgical incision and drainage of the mass, intravenous cefuroxime and metronidazole in the local hospital aggravated the skin lesions. Species identification was performed by observation of morphologic and biochemical characteristicsand sequencing of the internal transcribed spacer (ITS) and ß-tubulin (BT2). Treatment with oral and topical antifungal agents was effective with no relapse during the six months of clinical follow-up. CONCLUSIONS: Aspergillusis a opportunistic pathogenic fungus and its infection occurs mostly in patients with underlying conditions and immunocompromised statuses. So far no report of kerion-type scalp infection has been reported. The first case of kerion-type scalp mycosis caused by A. protuberus was described to highlight the importance of mycological examination that helps to recognize rare pathogenic fungi. Any boggy lesion with hair loss over the scalp and non-responsive to antibiotics should be suspected as resulting from fungal infection, and mycological examination should be performed, especially in children.


Assuntos
Aspergillus/isolamento & purificação , Micoses/diagnóstico , Couro Cabeludo/patologia , Antifúngicos/uso terapêutico , Aspergillus/classificação , Pré-Escolar , Feminino , Humanos , Hospedeiro Imunocomprometido , Micoses/tratamento farmacológico , Micoses/microbiologia , Filogenia , Couro Cabeludo/microbiologia
6.
Int Immunopharmacol ; 66: 336-346, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30521962

RESUMO

Acute lung injury (ALI), which is mainly triggered by infection, pneumonia, vasculitis, and sepsis, has no specific and effective therapy except for primary supportive treatment or bedside care. Excessive inflammation caused by innate immune cells is the major characteristic of ALI. Forsythoside B, a phenylethanoside compound, possesses good antioxidant and anti-bacterial properties in vivo and in vitro. In this study, the therapeutic potential of forsythoside B and its mechanism of action were investigated in a lipopolysaccharide (LPS)-induced ALI mouse model. The results showed that LPS-induced edema exudation and lung pathological changes in mice were significantly suppressed by forsythoside B pre-treatment. Furthermore, it also attenuated lung inflammation caused by LPS stimulation, evidenced by decreased inflammatory cell infiltration and down-regulated expression of cytokines, chemokines, and inducible enzymes. The anti-inflammation property of forsythoside B was confirmed in vitro using LPS-stimulated RAW 264.7 macrophages. Moreover, it alleviated LPS-induced inflammation by inhibiting the activation of TLR4/NF-κB signaling pathway in vivo and in vitro. In conclusion, the results demonstrated that forsythoside B protects against LPS-induced ALI by attenuating inflammatory cell infiltration and suppressing TLR4/NF-κB-mediated lung inflammation. Therefore, it might be a potential therapeutic agent for ALI caused by sepsis.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Ácidos Cafeicos/uso terapêutico , Glucosídeos/uso terapêutico , Inflamação/tratamento farmacológico , Pulmão/patologia , Macrófagos/efeitos dos fármacos , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Lipopolissacarídeos/imunologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Células RAW 264.7 , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo
7.
Pharmacol Res ; 137: 76-88, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30227260

RESUMO

T lymphocytes produced by the thymus are essential mediators of immunity. Accelerated thymic atrophy appears in the patients with administration of glucocorticoids (GCs) which are commonly-used drugs to treat autoimmune and infectious diseases, leading to dysregulation of immunity with manifestation of progressive diminution of new T cell production. However, there is no ideal method to overcome such side effects of GCs. In the current study, we proposed a composition of dexamethasone (DEX) and dihydromyricetin (DMY) derived from a medicinal plant, which could protect from DEX-induced thymus damage and simultaneously enhance the anti-inflammatory effect of DEX. In the current study, we found that DEX-damaged thymic cellularity and architecture, reduced thymocyte numbers, induced thymocyte apoptosis and dropped CD4+ and CD8+ double positive T cell numbers in thymus which was effectively improved by co-treatment with DMY. Quantification of signal joint TCR delta excision circles (TRECs) and Vß TCR spectratyping analysis were employed to determine the thymus function with indicated treatments. The results showed that DEX-impaired thymus output and decreased TCR cell diversity which was ameliorated by co-treatment with DMY. iTRAQ 2D LC-MS/MS was applied to analyze the proteomic profiling of thymus of mice treated with or without indicated agents, followed by informatics analysis to identify the correlated signaling pathway. After validated by Western blotting and Real-time PCR, we found that PPARγ-associated fatty acid metabolism was increased in the thymic tissues of the animals treated with DMY plus DEX than the animals treated with DEX alone. The agonist and antagonist of PPARγ were further employed to verify the role of PPARγ in the present study. Furthermore, DMY demonstrated a synergistic effect with co-administration of DEX on suppressing inflammation in vivo. Collectively, DMY relieved thymus function damaged by DEX via regulation of PPARγ-associated fatty acid metabolism. Our findings may provide a new strategy on protection of thymus from damage caused by GCs by using appropriate adjuvant natural agents through up-regulation of PPARγ-associated fatty acid metabolism.


Assuntos
Anti-Inflamatórios/farmacologia , Dexametasona/farmacologia , Ácidos Graxos/metabolismo , Flavonóis/farmacologia , Glucocorticoides/farmacologia , PPAR gama/metabolismo , Timo/efeitos dos fármacos , Animais , Anti-Inflamatórios/uso terapêutico , Dexametasona/uso terapêutico , Quimioterapia Combinada , Flavonóis/uso terapêutico , Glucocorticoides/uso terapêutico , Hipersensibilidade Tardia/tratamento farmacológico , Camundongos , Timo/metabolismo , Regulação para Cima/efeitos dos fármacos
8.
Mol Med Rep ; 16(5): 7175-7184, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28944829

RESUMO

The thymus is critical in establishing and maintaining the appropriate microenvironment for promoting the development and selection of T cells. The function and structure of the thymus gland has been extensively studied, particularly as the thymus serves an important physiological role in the lymphatic system. Numerous studies have investigated the morphological features of thymic involution. Recently, research attention has increasingly been focused on thymic proteins as targets for drug intervention. Omics approaches have yielded novel insights into the thymus and possible drug targets. The present review addresses the signaling and transcriptional functions of the thymus, including the molecular mechanisms underlying the regulatory functions of T cells and their role in the immune system. In addition, the levels of cytokines secreted in the thymus have a significant effect on thymic functions, including thymocyte migration and development, thymic atrophy and thymic recovery. Furthermore, the regulation and molecular mechanisms of stress­mediated thymic atrophy and involution were investigated, with particular emphasis on thymic function as a potential target for drug development and discovery using proteomics.


Assuntos
Citocinas/metabolismo , Transdução de Sinais , Linfócitos T/metabolismo , Timo/metabolismo , Animais , Movimento Celular , Humanos , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Timo/citologia
9.
Oncotarget ; 8(21): 34223-34235, 2017 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-27626700

RESUMO

The efficacious practice of precision personalized medicine requires a more exact understanding of the molecular mechanisms of drug, hence then it is necessary to identify the binding site of the drugs derived from natural sources. In the study, we investigated the suppressive effect and underlying mechanism of isoliquiritigenin (2',4',4-trihydroxychalcone; ILG), a phyto-flavonoid, on human T lymphocyte activation in vitro and in vivo. The results showed that ILG dose-dependently suppressed human T cell activation via suppressing IκBα phosphorylation and degradation, NF-κB nuclear translocation and IKKß activity. Molecular docking results predicted that cysteine 46 (Cys-46) is probably the binding site of ILG on IKKß, and this prediction has been validated by competition assay and kinase assay. To further verify the binding site of this compound in vivo, IKKßC46A transgenic (IKKßC46A) mice were generated. We found that ILG had a less potent immune-suppressive effect in homozygous IKKßC46A mice than IKKß wild type (IKKß wt) littermates with the delay-type hypersensitivity (DTH), suggesting that ILG cannot significantly suppress the inflammation due to the mutation of Cys-46 in the transgenic mice. Collectively, our findings indicate that the ILG inhibited T cell activation in vivo and in vitro via directly binding to IKKß Cys46.


Assuntos
Chalconas/administração & dosagem , Cisteína/metabolismo , Inibidores Enzimáticos/administração & dosagem , Quinase I-kappa B/química , Quinase I-kappa B/metabolismo , Linfócitos T/efeitos dos fármacos , Animais , Sítios de Ligação/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Chalconas/farmacologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Células HEK293 , Humanos , Quinase I-kappa B/genética , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Modelos Moleculares , Simulação de Acoplamento Molecular , Fosforilação/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Proteólise , Linfócitos T/citologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-23762128

RESUMO

The key role of T cells has been elaborated in mediating immune responses and pathogenesis of human inflammatory and autoimmune conditions. In the current study the effect of shikonin, a compound isolated from a medicinal plant, on inhibition of T-cell activation was firstly examined by using primary human T lymphocytes isolated from buffy coat. Results showed that shikonin dose dependently suppressed T-cell proliferation, IL-2 and IFN- γ secretion, CD69 and CD25 expression, as well as cell cycle arrest activated by costimulation of PMA/ionomycin or OKT-3/CD28 monoclonal antibodies. Moreover, these inhibitory responses mediated by shikonin were found to be associated with suppression of the NF- κ B signaling pathway via inhibition of the IKK α / ß phosphorylation, I κ B- α phosphorylation and degradation, and NF- κ B nuclear translocation by directly decreasing IKK ß activity. Moreover, shikonin suppressed JNK phosphorylation in the MAPKs pathway of T cells. In this connection, we conclude that shikonin could suppress T lymphocyte activation through suppressing IKK ß activity and JNK signaling, which suggests that shikonin is valuable for further investigation as a potential immunosuppressive agent.

11.
Environ Toxicol Pharmacol ; 33(2): 181-90, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22222560

RESUMO

Gambogenic acid, identified from Gamboge, is responsible for anti-tumor effects, and has been shown to be a potential molecule against human cancers. In this study, the molecular mechanism of gambogenic acid-induced apoptosis in HepG2 cells was investigated. Gambogenic acid significantly inhibited cell proliferation and induced apoptosis. Acridine orange/ethidium bromide (AO/EB) staining was used to observe apoptosis, and then confirmed by transmission electron microscopy. Gambogenic acid induced apoptosis and morphological changes in mitochondria, and intracellular reactive oxygen species (ROS) and mitochondrial membrane permeabilization (MMP) in mitochondrial apoptosis pathway were also examined. Results showed that the levels of phospho-p38 and its downstream phospho-Erk1/2 of HepG2 cells increased in time- and concentration-dependent manners after gambogenic acid treatments. Additionally, gambogenic acid increased expression ratio of Bcl-2/Bax in mRNA levels, Western blotting analysis also further confirmed the reduced level of Bcl-2 and increase the expression level of Bax in HepG2 cells. These results indicated that gambogenic acid induced mitochondrial oxidative stress and activated caspases through a caspase-3 and caspase-9-dependent apoptosis pathway. Moreover, gambogenic acid mediated apoptosis and was involved in the phospho-Erk1/2 and phospho-p38 MAPK proteins expression changes in HepG2 cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/enzimologia , Neoplasias Hepáticas/enzimologia , Mitocôndrias/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Terpenos/farmacologia , Xantonas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Western Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Caspase 3/metabolismo , Caspase 9/metabolismo , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Microscopia Eletrônica de Transmissão , Mitocôndrias/enzimologia , Mitocôndrias/patologia , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Xantenos , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
12.
J Asian Nat Prod Res ; 13(11): 993-1002, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22007630

RESUMO

Gamboge is a dry resin secreted from Garcinia hanburryi, and gambogenic acid (GNA) is one of the main active compounds of gamboge. We have previously demonstrated the anticancer activity of GNA in A549 cells and pointed out its potential effects in anticancer therapies. Previous studies reported that GNA induced apoptosis in many cancer cell lines and inhibited A549 tumor growth in xenograft of nude mice in vivo. However, the anticancer mechanism of GNA has still not been well studied. In this paper, we have investigated whether GNA-induced apoptosis is critically mediated by the p38 mitogen-activated protein kinase (MAPK) pathway. Our findings revealed that GNA could induce apoptosis, inhibit proliferation, down-regulate the expression of p38 and MAPK, increase the activations of caspase-9, caspase-3, and cytochrome c release. Furthermore, using SB203580, an adenosine triphosphate-competitive inhibitor of p38 MAPK, inhibit the expression of p-p38 and the experimental results show that it may promote the occurrence of apoptosis induced by GNA. Taken together, these results suggested that up-regulation of the p38 MAPK cascade may account for the activation of GNA-induced apoptosis.


Assuntos
Garcinia/química , Imidazóis/farmacologia , Piridinas/farmacologia , Terpenos/farmacologia , Xantonas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 9/metabolismo , Citocromos c/metabolismo , Humanos , Camundongos , Estrutura Molecular , Terpenos/química , Regulação para Cima/efeitos dos fármacos , Xantenos , Xantonas/química , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacos
13.
Eur J Pharmacol ; 652(1-3): 23-32, 2011 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-21118682

RESUMO

In the present study, Gambogenic acid exhibits potential anti-tumor activity in several cancer cell lines. However, Gambogenic acid-induced apoptosis mechanism is not well understood. Here, we report that Gambogenic acid was capable to induce CNE-1 cells apoptosis and caused mitochondrial and endoplasmic reticulum injury, analyzed via transmission electron microscopy and acridine orange/ethidium bromide (AO/EB) double staining. To quantitatively analyze apoptosis, through the propidium iodide (PI)/Annexin V-FITC double staining to detect cell apoptosis, PI staining of the cell cycle distribution. To further explore the potential mechanism of Gambogenic acid mediated apoptosis in CNE-1 cells, we also examined mitochondrial oxidative stress in the levels of reactive oxygen species, the release of cytochrome c, intracellular Ca(2+) concentration and mitochondrial membrane potential by flow cytometry. Moreover, Gambogenic acid could result in a time and concentration-dependent decrease in Phospho-Akt expression, basal expression levels of Akt change was not obvious, In addition, we detected Bcl-2 family including Bcl-2, Bax and Bad expression in mRNA level. This resulted in a decrease of Bcl-2 and Bad increased in CNE-1 cells after Gambogenic acid treatment. Overall, our results indicated that Gambogenic acid mediated apoptosis through inactivation of Akt, accompanied with mitochondrial oxidative stress and cross-talk with Bcl-2 family in the process of apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Proteína Oncogênica v-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Terpenos/farmacologia , Xantonas/farmacologia , Carcinoma , Proliferação de Células/efeitos dos fármacos , Humanos , Mitocôndrias/metabolismo , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Estresse Oxidativo , Transdução de Sinais/efeitos dos fármacos , Células Tumorais Cultivadas , Xantenos , Proteína X Associada a bcl-2/metabolismo
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