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1.
J Cancer Res Clin Oncol ; 146(7): 1751-1764, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32377840

RESUMO

PURPOSE: Although important for apoptosis, the signaling pathway involving MOAP-1(Modulator of Apoptosis 1), RASSF1A (RAS association domain family 1A), and Bax (Bcl-2 associated X protein) is likely to be dysfunctional in many types of human cancers due to mechanisms associated with gene mutation and DNA hyper-methylation. The purpose of the present study was to assess the potential impact of generating physiologically relevant signaling pathway mediated by MOAP-1, Bax, and RASSF1A (MBR) in cancer cells and chemo-drug resistant cancer cells. METHODS: The tricistronic expression construct that encodes MOAP-1, Bax, and RASSF1A (MBR) or its mutant, MOAP-1∆BH3L, Bax and RASSF1A (MBRX) was expressed from an IRES (Internal Ribosome Entry Site)-based tricistronic expression vector in human breast cancer cells, including MCF-7, MCF-7-CR (cisplatin resistant) and triple negative breast cancer cells, BMET05, for functional characterization through in vitro and in vivo models. RESULTS: Transient expression of MBR potently promoted dose-dependent apoptotic signaling and chemo-sensitization in the cancer cells, as evidenced by loss of cell viability, nuclei condensation and Annexin-V positive staining while stable expression of MBR in MCF-7 cells significantly reduced the number of MBR stable clone by 86% and the stable clone exhibited robust chemo-drug sensitivity. In contrast, MBRX stable clone exhibited chemo-drug resistance while transiently over-expressed MOAP-1ΔBH3L inhibited the apoptotic activity of MBR. Moreover, the spheroids derived from the MBR stable clone displayed enhanced chemo-sensitivity and apoptotic activity. In mouse xenograft model, the tumors derived from MBR stable clone showed relatively high level of tumor growth retardation associated with the increase in apoptotic activity, leading to the decreases in both tumor weight and volume. CONCLUSIONS: Expression of MBR in cancer cells induces apoptotic cell death with enhanced chemo-sensitization requiring the BH3L domain of MOAP-1. In animal model, the expression of MBR significantly reduces the growth of tumors, suggesting that MBR is a potent apoptotic sensitizer with potential therapeutic benefits for cancer treatment.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose/genética , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Domínios e Motivos de Interação entre Proteínas , Proteínas Supressoras de Tumor/genética , Proteína X Associada a bcl-2/genética , Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Proteínas Reguladoras de Apoptose/química , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Modelos Animais de Doenças , Genes Reporter , Humanos , Camundongos , Modelos Biológicos , Ligação Proteica , Proteínas Supressoras de Tumor/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína X Associada a bcl-2/metabolismo
2.
Pestic Biochem Physiol ; 166: 104580, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32448426

RESUMO

To determine the possible role of apoptosis in the development of paraoxon-induced brain damage, we evaluated expression of apoptosis-related proteins, the extent of neuronal damage, and activation of astrocytes in rat hippocampus. Adult male Wistar rats were intraperitoneally injected with one of three doses of paraoxon (0.3, 0.7, or 1 mg/kg) or corn oil (vehicle). After 14 or 28 days, expression of apoptosis-related proteins, including B-cell leukemia/lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), and caspase-3, as well as the number of neurons and glial fibrillary acidic protein (GFAP) positive cells in hippocampus were examined by western blot, cresyl blue staining, and immunohistochemistry, respectively. After 14 and 28 days, Bax and caspase-3 proteins were significantly increased in rats receiving 0.7 and 1 mg/kg of paraoxon. A significant decrease in Bcl-2 protein levels was also observed in 0.7 and 1 mg/kg groups after 14 days and in 1 mg/kg group after 28 days. Animals treated with 1 mg/kg of paraoxon showed a significant decrease in the number of neurons in the CA1 area. Also, those treated with 0.7 and 1 mg/kg of paraoxon showed an increase in the number of GFAP positive cells in both CA1 and CA3 areas as well as a significant decrease in survived neurons in the CA3 area. Our results indicated that neuronal damage induced by convulsive doses of paraoxon in rat hippocampus is mediated in part through apoptosis mechanism. Activation of astrocytes might lead to reduced extent of damage and damage and consequently increased neuronal survival.


Assuntos
Hipocampo , Paraoxon , Animais , Apoptose , Masculino , Ratos , Ratos Wistar , Proteína X Associada a bcl-2
3.
PLoS One ; 15(4): e0223208, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32302311

RESUMO

The aim of this study was to investigate whether exogenous erythropoietin (EPO) administration attenuates N-methyl-D-aspartate (NMDA)-mediated excitotoxic retinal damage in Wistar rats. The survival rate of retinal ganglion cells (RGCs) were investigated by flat mount analysis and flow cytometry. A total of 125 male Wistar rats were randomly assigned to five groups: negative control, NMDA80 (i.e., 80 nmoles NMDA intravitreally injected), NMDA80 + 10ng EPO, NMDA80 + 50ng EPO, and NMDA80 + 250ng EPO. The NMDA80 + 50ng EPO treatment group was used to evaluate various administrated points (pre-/co-/post- administration of NMDA80). Meanwhile, the transferase dUTP Nick-End Labeling (TUNEL) assay of RGCs, the inner plexiform layer (IPL) thickness and the apoptotic signal transduction pathways of µ-calpain, Bax, and caspase 9 were assessed simultaneously using an immunohistochemical method (IHC). When EPO was co-administered with NMDA80, attenuated cell death occurred through the downregulation of the apoptotic indicators: µ-calpain was activated first (peak at ~18hrs), followed by Bax and caspase 9 (peak at ~40hrs). Furthermore, the images of retinal cross sections have clearly demonstrated that thickness of the inner plexiform layer (IPL) was significantly recovered at 40 hours after receiving intravitreal injection with NMDA80 and 50ng EPO. Exogenous EPO may protect RGCs and bipolar cell axon terminals in IPL by downregulating apoptotic factors to attenuate NMDA-mediated excitotoxic retinal damage.


Assuntos
Apoptose , Eritropoetina/farmacologia , N-Metilaspartato/farmacologia , Fármacos Neuroprotetores/farmacologia , Células Ganglionares da Retina/efeitos dos fármacos , Animais , Caspase 9/genética , Caspase 9/metabolismo , Regulação para Baixo , Masculino , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/agonistas , Receptores de N-Metil-D-Aspartato/metabolismo , Células Ganglionares da Retina/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
4.
Zhongguo Zhong Yao Za Zhi ; 45(6): 1418-1422, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32281356

RESUMO

Polyphyllin D is a steroid saponin monomer in Polyphyllin, with antibacterial, analgesic, sedative, anti-tumor and other pharmacological effects, but is rarely reported in pancreatic cancer. This study detected apoptosis-relevant indicators, in order to explore the effect of polyphyllin D on the proliferation and apoptosis of human pancreatic cancer Panc-1 cells and relevant mechanisms of action. After pancreatic cancer Panc-1 cells were treated with polyphyllin D(0, 1, 2, 3, 4, 5 µg·µL~(-1)) for 24, 48 and 72 hours, CCK-8 method was used to detect the effect of polyphyllin D on the proliferation of pancreatic cancer Panc-1 cells. Flow cytometry was used to detect cell cycle and changes in mitochondrial membrane potential(MMP). The apoptosis was detected by Annexin V-FITC/PI staining, and Western blot was used to detect the protein expressions of cytochrome C(Cyto C), Bax, Bcl-2, cleaved caspase-3 and cleaved caspase-9. The results indicated that compared with the control group, polyphyllin D could inhibit the proliferative activity of Panc-1 cells in a time and concentration-dependent manner. Flow cytometry results showed that polyphyllin D could block the cells in S and G_2/M phase in a concentration manner, the MMP of the cells was significantly reduced, and the apoptosis rate increased with the concentration of polyphyllin D. Western blot results showed that polyphyllin D could concentration-dependently up-regulate the protein expression levels of Bax, Cyto C, cleaved caspase-3 and cleaved caspase-9, and down-regulate the protein expression level of Bcl-2. The above findings suggested that polyphyllin D could effectively inhibit the proliferation of Panc-1 cells, and its mechanism may be related to the blocking of cell growth cycle and the apoptosis induced by mitochondrial pathway.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose , Diosgenina/análogos & derivados , Neoplasias Pancreáticas/patologia , Saponinas/farmacologia , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Diosgenina/farmacologia , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo
5.
Chem Biol Interact ; 323: 109075, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32229109

RESUMO

The use of orchids in herbal medicine has a very long history. Dendrobium species are known to produce a variety of secondary metabolites such as phenanthrens, bibenzyls, fluorenones and sesquiterpenes, and alkaloids and are responsible for their wide variety of medicinal properties. For decades, bibenzyls, which are the main bioactive components derived from Dendrobium species, have been subjected to extensive investigation as likely candidates for cancer treatment. The present study was undertaken to investigate the effect of moscatilin, a bibenzyl derivative from the orchid Dendrobium loddigesii on human melanoma cells. In A375 cells compound moscatilin showed a clear dose-response relationship in the range of 6.25-50 µM concentrations. In addition, we demonstrated an apoptotic response after treatment of cancer cells with this bibenzyl compound at 6.25 and 12.5 µM concentrations that probably involves PTEN activity, inhibition of Hsp70 expression and reactive oxygen species production. Alternatively, the inhibition of the caspase cascade at higher concentrations, 25 and 50 µM, correlated with additional reactive oxygen species increase, probably switched the mode of moscatilin-induced cell death from apoptosis to necrosis.


Assuntos
Apoptose/efeitos dos fármacos , Compostos de Benzil/uso terapêutico , Dendrobium/química , Melanoma/tratamento farmacológico , Melanoma/patologia , Compostos de Benzil/química , Compostos de Benzil/farmacologia , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , DNA de Neoplasias/metabolismo , Glutationa/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismo
6.
Chin J Nat Med ; 18(3): 226-233, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32245593

RESUMO

Shenfu injection (SFI), a Chinese medicinal product, shows potent efficacy in treating sepsis. The aim of the present study was to clarify the protective effects of SFI against lipopolysaccharide (LPS)-induced myocardial inflammation and apoptosis. Experiments were carried out in Sprague-Dawley (SD) rats treated with LPS or LPS + SFI, and in H9C2 cardiomyocytes. The sepsis-associated myocardial inflammation and apoptosis was induced by the intraperitoneal injection of LPS (20 mg·kg-1). SFI attenuated the increased expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß induced by LPS both in serum and heart. In LPS group, cell viability was reduced, and reversed after SFI administration. LPS treatment increased the expression levels of cleaved-caspase 3 and Bax, and those of Bcl2 and Bcl2/Bax. These two trends were reversed by SFI administration. The expression levels of phosphorylated mitogen-activated protein kinase kinase (p-MEK) and phosphorylated extracellular regulated protein kinases (p-ERK) were increased by LPS, and reversed by SFI. MEK inhibitor U0126 attenuated the apoptosis induced by LPS. These results indicate that SFI could treat LPS-induced cardiac dysfunction. In conclusion, SFI attenuates the inflammation and apoptosis induced by LPS via downregulating the MEK and ERK signaling pathways.


Assuntos
Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Miocardite/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Sepse/tratamento farmacológico , Animais , Caspase 3/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos , Masculino , Miocárdio/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/metabolismo
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 29-33, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027249

RESUMO

OBJECTIVE: To explore whether BAX plays a role in the development of Philadelphia chromosome-positive leukemia and related mechanisms. METHODS: Target-gene knockout mice were used as bone marrow cell donors. Retrovirus over-expressing BCR-ABL were packaged. BCR-ABL-induced B-ALL mouse model was established through donor's B cells transfected by the retrovirus and the B cells over-expressing BCR-ABL were given to the receptor mice by tail vein injection. Western blot was used to detect the protein express and flow cytometry was used to analyze the B cell subpopulations in BAX-/- and WT mouse bone marrows. Kaplan-Meier analysis was used to estimate the survival of diseased mice. RESULTS: BAX deletion caused faster development of BCR-ABL-induced leukemia in vitro and in vivo. BCR-ABL increased BCL-2 expression and enhanced BCL-2/BAX heterodimer formation. CONCLUSION: The BAX deletion can accelerate the disease progression of BCR-ABL induced B-ALL.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Animais , Células da Medula Óssea , Progressão da Doença , Proteínas de Fusão bcr-abl , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Camundongos , Proteína X Associada a bcl-2
8.
PLoS Pathog ; 16(2): e1008297, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32032391

RESUMO

Hantaviruses, zoonotic RNA viruses belonging to the order Bunyavirales, cause two severe acute diseases in humans, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Hantavirus-infected patients show strong cytotoxic lymphocyte responses and hyperinflammation; however, infected cells remain mostly intact. Hantaviruses were recently shown to inhibit apoptosis in infected cells. By inhibiting granzyme B- and TRAIL-mediated apoptosis, hantaviruses specifically and efficiently inhibit cytotoxic lymphocyte-mediated killing of infected cells. Hantaviruses also strongly inhibit apoptosis triggered intrinsically; i.e., initiated through intracellular activation pathways different from those used by cytotoxic lymphocytes. However, insights into the latter mechanisms are currently largely unknown. Here, we dissected the mechanism behind how hantavirus infection, represented by the HFRS-causing Hantaan virus and the HPS-causing Andes virus, results in resistance to staurosporine-induced apoptosis. Less active caspase-8 and caspase-9, and consequently less active caspase-3, was observed in infected compared to uninfected staurosporine-exposed cells. While staurosporine-exposed uninfected cells showed massive release of pro-apoptotic cytochrome C into the cytosol, this was not observed in infected cells. Further, hantaviruses prevented activation of BAX and mitochondrial outer membrane permeabilization (MOMP). In parallel, a significant increase in levels of the pro-survival factor BCL-2 was observed in hantavirus-infected cells. Importantly, direct inhibition of BCL-2 by the inhibitor ABT-737, as well as silencing of BCL-2 by siRNA, resulted in apoptosis in staurosporine-exposed hantavirus-infected cells. Overall, we here provide a tentative mechanism by which hantaviruses protect infected cells from intrinsic apoptosis at the mitochondrial level by inducing an increased expression of the pro-survival factor BCL-2, thereby preventing MOMPs and subsequent activation of caspases. The variety of mechanisms used by hantaviruses to ensure survival of infected cells likely contribute to the persistent infection in natural hosts and may play a role in immunopathogenesis of HFRS and HPS in humans.


Assuntos
Apoptose , Febre Hemorrágica com Síndrome Renal/metabolismo , Potencial da Membrana Mitocondrial , Membranas Mitocondriais/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Regulação para Cima , Células A549 , Caspases/genética , Caspases/metabolismo , Citocromos c/genética , Citocromos c/metabolismo , Febre Hemorrágica com Síndrome Renal/patologia , Humanos , Membranas Mitocondriais/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
9.
Biosci Trends ; 14(1): 23-34, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32092745

RESUMO

The roots of Angelica dahurica have long been used as a traditional medicine in Korea to treat various diseases such as toothache and cold. In this study, we investigated the effect of ethanol extract from the roots of this plant on metastatic melanoma, a highly aggressive skin cancer, in B16F10 melanoma cells and B16F10 cell inoculated-C57BL/6 mice. Our results showed that the ethanol extracts of Angelicae dahuricae Radix (EEAD) suppressed cell growth and induced apoptotic cell death in B16F10 cells. EEAD also activated the mitochondria-mediated intrinsic apoptosis pathway, with decreased mitochondrial membrane potential, and increased production of intracellular reactive oxygen species and ration of Bax/Bcl-2 expression. Furthermore, EEAD reduced the migration, invasion, and colony formation of B16F10 cells through the reduced expression and activity of matrix metalloproteinase (MMP)-2 and -9. In addition, in vivo results demonstrated that oral administration of EEAD inhibited lactate dehydrogenase activity, hepatotoxicity, and nephrotoxicity without weight loss in B16F10 cell inoculated-mice. Importantly, EEAD was able to markedly suppress lung hypertrophy, the incidence of B16F10 cells lung metastasis, and the expression of tumor necrosis factor-alpha in lung tissue. Taken together, our findings suggest that EEAD may be useful for managing metastasis and growth of malignant cancers, including melanoma.


Assuntos
Angelica/química , Melanoma Experimental/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Apoptose , Linhagem Celular Tumoral , Hipertrofia , L-Lactato Desidrogenase/antagonistas & inibidores , Pulmão/patologia , Neoplasias Pulmonares , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Metástase Neoplásica/prevenção & controle , Raízes de Plantas/química , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/metabolismo
10.
Zhongguo Zhen Jiu ; 40(2): 179-84, 2020 Feb 12.
Artigo em Chinês | MEDLINE | ID: mdl-32100505

RESUMO

OBJECTIVE: To observe the effects of fast-twisting long-retaining (FTLR) acupuncture therapy on apoptosis of vestibular nucleus and expression of Caspase-3, Bcl-2 and Bax in rats with vertigo induced by posterior circulation ischemia. METHODS: A total of 70 healthy SD rats were randomly divided into a sham operation group, a model group, a medication group, a regular acupuncture group and a FTLR acupuncture group, 14 rats in each group. The rats in the model group, medication group, regular acupuncture group and FTLR acupuncture group were intervented with surgical ligation of the right common carotid artery (CCA) and the right subclavian artery (SCA) to establish the model of vertigo induced by posterior circulation ischemia; in the sham operation group, the right CCA and the right SCA were separated without ligation. The rats in the medication group were treated with gavage of flunarizine hydrochloride suspension (10 mL/kg). "Baihui" (GV 20), "Shuaigu" (GB 8) and "Fengchi" (GB 20) were selected in the two acupuncture groups. The rats in the regular acupuncture group were treated with routine acupuncture and the needles were retained for 30 min, while the rats in the FTLR acupuncture group were treated with quick twist (200-300 times/min) for 1 min and the needles were retained for 60 min. The rats in the sham operation group and the model group received no intervention. All the intervention was provided once a day for 10 days. The decline rate of local blood flow in vestibular nucleus was observed; the apoptosis of vestibular nucleus was observed by TUNEL method; the expression of Caspase-3, Bcl-2 and Bax proteins were detected by immunohistochemistry. RESULTS: Compared with the sham operation group, the decline rate of local blood flow in the right vestibular nucleus was significantly increased in the model group (P<0.01), and the apoptosis index (AI) of vestibular nucleus was significantly increased (P<0.01). Compared with the model group, the decline rates of local blood flow in the right vestibular nucleus in the two acupuncture groups and medication group were significantly reduced (P<0.01), and the AIs of vestibular nucleus cells were significantly reduced (P<0.01). The decline rate of local blood flow in the right vestibular nucleus in the FTLR acupuncture group was lower than those in the medication group and the regular acupuncture group (P<0.01, P<0.05), and the AI of vestibular nucleus was lower than those in the regular acupuncture group and the medication group (P<0.05). Compared with the sham operation group, the expression of Bcl-2 in the vestibular nucleus was significantly decreased in the model group (P<0.01), and the expressions of Bax and Caspase-3 were significantly increased (P<0.01). Compared with the model group, the expressions of Bcl-2 in the vestibular nucleus were significantly increased in the two acupuncture groups and medication group (P<0.01), and the expressions of Bax and Caspase-3 were significantly reduced (P<0.01). The expression of Bcl-2 in the vestibular nucleus in the FTLR acupuncture group was higher than those in the regular acupuncture group and the medication group (P<0.05), and the expressions of Bax and Caspase-3 were lower than those in the regular acupuncture group and the medication group (P<0.05). CONCLUSION: The FTLR acupuncture therapy could effectively inhibit the apoptosis of vestibular nucleus in rats with vertigo induced by posterior circulation ischemia, and its mechanism may be related to improving the blood supply of vestibular nucleus and regulating the expressions of Caspase-3, Bcl-2 and Bax proteins.


Assuntos
Terapia por Acupuntura , Apoptose , Isquemia/complicações , Vertigem/terapia , Núcleo Vestibular Lateral/metabolismo , Animais , Caspase 3/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Vertigem/etiologia , Proteína X Associada a bcl-2/metabolismo
11.
Life Sci ; 248: 117452, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32088214

RESUMO

AIMS: The aim of this study was to elucidate the signaling pathway involved in the anti-aging effect of tropisetron and to clarify whether it affects mitochondrial oxidative stress, apoptosis and inflammation in the aging mouse brain by upregulating Sirtuin 1 or silent information regulator 1 (SIRT1). MATERIALS AND METHODS: Aging was induced by d-galactose (DG) at the dose of 200 mg/kg body weight/day subcutaneously injected to male mice for six weeks. Tropisetron was simultaneously administered intraperitoneally once a day at three various doses (1, 3 and 5 mg/kg body weight). Oxidative stress and mitochondrial dysfunction markers were evaluated. Nitric oxide (NO) and pro-inflammatory cytokines levels including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were studied. Besides, the expressions of apoptosis-associated genes (Bax and Bcl-2) and the aging-related gene (SIRT1) were determined by the real time polymerase chain reaction (RT-PCR). In addition, histopathological alterations were assessed. KEY FINDINGS: Tropisetron reversed the induction of oxidative damage, mitochondrial dysfunction and overproduction of inflammatory mediators induced by DG in the brain tissue. In addition, tropisetron suppressed DG-induced apoptosis and found to significantly elevate SIRT1 gene expression. Besides, tropisetron could markedly alleviate DG-induced abnormal changes in the brain morphology. SIGNIFICANCE: Tropisetron exhibited anti-aging effects in the context of DG-induced senescence in mouse brain through various pathways. Our results suggest that tropisetron may attenuate DG-induced brain aging via SIRT1 signaling activation.


Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Antagonistas do Receptor 5-HT3 de Serotonina/farmacologia , Sirtuína 1/genética , Tropizetrona/farmacologia , Envelhecimento/genética , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Encéfalo/metabolismo , Encéfalo/patologia , Esquema de Medicação , Galactose/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação , Injeções Intraperitoneais , Injeções Subcutâneas , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
12.
Life Sci ; 248: 117466, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32101760

RESUMO

AIMS: Nanoparticles (NPs)-based drugs have been recently introduced to improve the efficacy of current therapeutic strategies for the treatment of cancer; however, the molecular mechanisms by which a NP interacts with cellular systems still need to be delineated. Here, we utilize the autophagic potential of TiO2 NPs for improving chemotherapeutic effects of 5-fluorouracil (5-FU) in human AGS gastric cells. MATERIALS AND METHODS: Cell growth and viability were determined by trypan blue exclusion test and MTT assay, respectively. Vesicular organelles formation was evaluated by acridine orange staining of cells. Cell cycle and apoptosis were monitored by flow cytometry. Reactive oxygen species (ROS) level were measured by DCHF-DA staining. Autophagy was examined by q-PCR and western blotting. Molecular docking was used for studying NP interaction with autophagic proteins. KEY FINDINGS: TiO2 NPs increase ROS production, impair lysosomal function and subsequently block autophagy flux in AGS cells. In addition, the autophagy blockade induced by non-toxic concentrations of TiO2 NPs (1 µg/ml) can promote cytotoxic and apoptotic effects of 5-FU in AGS cells. SIGNIFICANCE: These results confirm the beneficial effects of TiO2 NPs in combination with chemotherapy in in vitro model of gastric cancer, which may pave the way to develop a possible solution to circumvent chemoresistance in cancer.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica , Nanopartículas/química , Titânio/farmacologia , Antimetabólitos Antineoplásicos/química , Apoptose/efeitos dos fármacos , Apoptose/genética , Autofagia/genética , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína 7 Relacionada à Autofagia/genética , Proteína 7 Relacionada à Autofagia/metabolismo , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Vesículas Citoplasmáticas/efeitos dos fármacos , Vesículas Citoplasmáticas/metabolismo , Sinergismo Farmacológico , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Fluoruracila/química , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Humanos , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Proteínas Associadas aos Microtúbulos/antagonistas & inibidores , Proteínas Associadas aos Microtúbulos/química , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Simulação de Acoplamento Molecular , Nanopartículas/ultraestrutura , Conformação Proteica , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Proteína Sequestossoma-1/antagonistas & inibidores , Proteína Sequestossoma-1/genética , Proteína Sequestossoma-1/metabolismo , Titânio/química , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
13.
Acta Biochim Biophys Sin (Shanghai) ; 52(1): 26-37, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31889181

RESUMO

Chlorine is shown to possess anti-gastric ulcer activity, since it can inactivate Helicobacter pylori, which is regarded as one of the most common risk factors for causing gastric problems. In the current study, the gastroprotective property of a novel dichloro-substituted Schiff base complex, 2, 2'- [-1, 2-cyclohexanediylbis(nitriloethylidyne)] bis(4-chlorophenol) (CNCP), against alcohol-induced gastric lesion in SD rats was assessed. SD rats were divided into four groups, i.e. normal, ulcer control, testing, and reference groups. Ulcer area, gastric wall mucus, and also gastric acidity of the animal stomachs were measured. In addition, antioxidant activity of CNCP was evaluated and its safe dose was identified. Immunohistochemistry staining was also carried to evaluate two important proteins, i.e. Bcl2-associated X protein (Bax) and heat shock protein 70 (HSP70). Moreover, the activities of super oxide dismutase and catalase, as well as the levels of prostaglandin E2 (PGE2) and malondialdehyde (MDA) were also measured. Antioxidant activity of CNCP was approved via the aforementioned experiments. Histological evaluations showed that the compound possesses stomach epithelial defense activity. Additionally, periodic acid-Schiff staining exhibited over-expression of HSP70 and down-expression of Bax protein in the CNCP-treated rats. Moreover, CNCP caused deceased MDA level and elevated PGE2 level, and at the same time increased the activities of the two enzymes.


Assuntos
Antioxidantes/uso terapêutico , Proteínas de Choque Térmico HSP70/metabolismo , Bases de Schiff/toxicidade , Bases de Schiff/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Úlcera Gástrica/tratamento farmacológico , Proteína X Associada a bcl-2/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Catalase/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Clorofenóis/química , Dinoprostona/metabolismo , Modelos Animais de Doenças , Etanol/efeitos adversos , Etanol/farmacologia , Feminino , Fibroblastos/metabolismo , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Testes de Função Renal , Testes de Função Hepática , Masculino , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Bases de Schiff/química , Úlcera Gástrica/induzido quimicamente , Superóxido Dismutase/metabolismo
14.
Cancer Sci ; 111(4): 1344-1356, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31960547

RESUMO

5-Fluorouracil-based therapy remains the main approach in colorectal cancer, even though there are still some drawbacks, such as chemoresistance. In this study we combined 5-fluorouracil encapsulated in long-circulating liposomes with simvastatin, also encapsulated in long-circulating liposomes, that was previously proved to exert antitumor actions on the same tumor model. The production of angiogenic/inflammatory proteins was assessed by protein array and the production of markers for tumor aggressiveness (Bcl-2, Bax, and nuclear factor [NF]-κB) were determined by western blot analysis. Intratumor oxidative stress was evaluated through measurement of malondialdehyde level by HPLC, and through spectrophotometric analysis of catalytic activity of catalase and of total antioxidant capacity. Immunohistochemical analysis of tumors for CD31 expression was assessed. Intratumor activity of MMP-2 by gelatin zymography was also carried out. Our results revealed that combined therapies based on liposomal formulations exerted enhanced antitumor activities compared with combined treatment with free drugs. Sequential treatment with liposomal simvastatin and liposomal 5-fluorouracil showed the strongest antitumor activity in C26 colon carcinoma in vivo, mainly through inhibition of tumor angiogenesis. Important markers for cancer progression (Bcl-2, Bax, NF-κB, and intratumor antioxidants) showed that liposomal simvastatin might sensitize C26 cells to liposomal 5-fluorouracil treatment in both regimens tested. The outcome of simultaneous treatment with liposomal formulations was superior to sequential treatment with both liposomal types as the invasive capacity of C26 tumors was strongly increased after the latest treatment. The antitumor efficacy of combined therapy in C26 colon carcinoma might be linked to the restorative effects on proteins balance involved in tumor angiogenesis.


Assuntos
Carcinoma/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Sinvastatina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Carcinoma/genética , Carcinoma/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Lipossomos/farmacologia , Camundongos , NF-kappa B/genética , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína X Associada a bcl-2/genética
15.
World Neurosurg ; 136: e460-e468, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31953094

RESUMO

BACKGROUND: Allicin can suppress liver and cardiac fibrosis; thus, we hypothesized that it might prevent scar tissue from extensive epidural fibrosis after laminectomy. METHODS: Human epidural scar fibroblasts were isolated from surgical specimens and treated with allicin at a gradient of concentrations. Morphology, viability, migration rate, cell cycle, and apoptosis rate were measured by fluorescence microscope, Cell Counting Kit-8 assay, scratch assay, and flow cytometry. Western blot was used to measure the expression level of proliferation-related proteins. RESULTS: After treatment by allicin, cell viability (P = 0.042) and migration rate (P = 0.010 in scratch assay and P = 0.025 in transwell assay) decreased significantly in a dose-dependent manner. The percentage of G1 phase cells significantly decreased (P = 0.017), whereas the percentage of S phase cells (P = 0.096) and G2 phase cells (P = 0.038) significantly increased in a dose-dependent manner. Similarly, the percentage of apoptotic cells increased significantly in a dose-dependent manner (P = 0.036). Compared with the control group, the expression level of proliferating cell nuclear antigen protein (P = 0.081) and Bcl-2 protein (P = 0.029) significantly decreased, whereas the BAX protein level significantly increased (P = 0.017). CONCLUSIONS: Allicin can suppress human epidural scar fibroblast migration, induce cell apoptosis, and block cell proliferation at S phase and G2 phase.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cicatriz/patologia , Espaço Epidural/patologia , Fibroblastos/efeitos dos fármacos , Ácidos Sulfínicos/farmacologia , Biomarcadores/metabolismo , Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Fibroblastos/citologia , Fibrose/patologia , Humanos , Vértebras Lombares , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteína X Associada a bcl-2/metabolismo
16.
Lasers Med Sci ; 35(1): 71-78, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31049741

RESUMO

To investigate the killing effect and inducing apoptosis of 630-nm laser mediated by hematoporphyrin derivatives (HPD) on human lung adenocarcinoma A549 cells. The human lung adenocarcinoma A549 cells were incubated at random with different concentrations of HPD (5, 10, 12, 15, 20 µg/ml) for 4 h and then illuminated by 630-nm laser with different energy densities (25, 50, 75, 100 mW/cm2). And, meanwhile, the simple photosensitizer group, laser irradiation group, and blank control group were established. Then, CCK8, Hoechst 33258 staining, RT-PCR, and Western blot were employed. HPD-PDT proved no killing effect on the lung adenocarcinoma A549 cells with photosensitizer or laser irradiation alone. With the combination, the killing effect was obvious. CCK8 showed that the A549 cell viability in 15 µg/ml and 20 µg/ml HPD group as well as 50 mW/cm2, 75 mW/cm2, and 100 mW/cm2 power density group decreased significantly compared with the control group. Hoechst 33258 staining showed that with the increase of HPD concentration, the cells presented chromatin fixation and hyperchromatic nuclei. The Annexin V-FITC/PI double staining was used to detect the apoptosis rate, and the difference was statistically significant. RT-PCR and Western blot showed that the expression of Caspase-3 and Bax were significantly up-regulated. However, the Bcl-2 and Survivin were significantly down-regulated in the HPD-PDT group, while those of the other three groups showed no significant changes. HPD-PDT has a significant effect on A549 cells. The mechanism of action may be related to the upregulation of the expression of Caspase-3, Bax, and downregulation of the expression of Bcl-2 and Survivin.


Assuntos
Adenocarcinoma de Pulmão/patologia , Apoptose , Derivado da Hematoporfirina/farmacologia , Células A549 , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Caspase 3/genética , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Regulação para Baixo/efeitos dos fármacos , Humanos , Lasers , Neoplasias Pulmonares/patologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Survivina/genética , Survivina/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
17.
Acta Haematol ; 143(1): 51-59, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31434075

RESUMO

BACKGROUND: SAM domain- and HD domain-containing protein 1 (SAMHD1) is a cellular enzyme which is responsible for blocking replication in viruses and participates in the progression of many cancers. OBJECTIVE: The aim of this study was to correlate the expression level of SAMHD1 with other apoptotic and autophagic genes in acute myeloid leukemia (AML) patients. METHODS: In the present study, mRNA levels of SAMHD1 with other apoptotic and autophagic-related genes were evaluated in patients who were newly diagnosed with AML. RESULTS: SAMHD1, Bcl-xl, Bax, Bak, XIAP, and cIAP1 were downregulated in the AML group compared to the non-AML group (p < 0.05). SAMHD1 expression did not correlate with the other genes, while most apoptotic genes were positively correlated with each other. SAMHD1 expression was not associated with the blood routine or blast percentage of the AML patients, while Bax, Bak, cIAP2, and LC3 were significantly correlated with white blood cells. No statistically significant differences were found between the studied genes and prognosis stratifications, but Bcl-xl, Bak, cIAP1, and Mcl-1, LC3 were expressed at lower levels in the unfavorable AML group compared to the controls. CONCLUSION: SAMHD1 and Bcl-xl, Bax, Bak, XIAP, and cIAP1 were downregulated in AML patients, while there were no significant differences in the clinical characteristics and prognosis with reference to SAMHD1 expression.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Leucemia Mieloide Aguda/diagnóstico , Proteína 1 com Domínio SAM e Domínio HD/metabolismo , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteínas Reguladoras de Apoptose/genética , Regulação para Baixo , Feminino , Expressão Gênica , Humanos , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Leucócitos/citologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteína 1 com Domínio SAM e Domínio HD/genética , Taxa de Sobrevida , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Proteína Killer-Antagonista Homóloga a bcl-2/genética , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Proteína bcl-X/genética , Proteína bcl-X/metabolismo
18.
Food Chem Toxicol ; 135: 110925, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31676349

RESUMO

Manganese (Mn), an essential micronutrient, has the potential to induce apoptosis. The NT3/TrkC ligand/receptor pair known as part of the classic neurotrophic theory plays a critical role in neuronal survival. However, whether the NT3/TrkC-mediated signaling pathways are involved in Mn-induced apoptosis of cortical neurons remains unknown. The present study was designed to investigate the interactions between NT3/TrkC-mediated signaling pathways and Mn-induced apoptosis in cortical neurons. This study showed that subacute Mn exposure significantly increased the levels of pro-apoptotic Bax while decreasing the levels of anti-apoptotic Bcl 2 in the cortex compared with the corresponding control. Markedly reduced NT3 and TrkC levels along with decreased Ras/MAPK and PI3/Akt signaling in the cortex were observed following subacute Mn exposure. We further found increased levels of Bax, cleaved caspase-3, and the total apoptosis rate, and decreased levels of Bcl 2, NT3, TrkC, and Ras/MAPK and PI3/Akt signaling in Mn-treated primary cortical neurons. Pretreatment with hNT3 or Z-VAD-FAM ameliorated Mn-induced apoptosis by increasing the levels of NT3 and TrkC and its Ras/MAPK and PI3/Akt signaling pathways. Taken together, our findings clearly indicate that NT3/TrkC and mediated Ras/MAPK and PI3/Akt signaling pathways play a crucial role in Mn-induced neurotoxicity.


Assuntos
Córtex Cerebral/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Manganês/toxicidade , Neurônios/efeitos dos fármacos , Neurotrofina 3/metabolismo , Receptor trkC/metabolismo , Animais , Apoptose/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteínas ras/metabolismo
19.
Mol Cell Biochem ; 463(1-2): 115-126, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31654185

RESUMO

Shrm4 is a protein that is exclusively expressed in polarized tissues. The physiological function of Shrm4 in the brain was required to be elucidated. Thus, we aimed to explore how the Shrm4-mediated gamma-aminobutyric acid (GABA) pathway affected neural stem cells (NSCs). At first, the Nestin expression in cultured NSCs was identified. After determination of the interaction of Shrm4 and GABAB1, a series of in vitro experiment were performed to detect cell proliferation, the ability of cell colony formation, degree that NSCs differentiated into neurons, the apoptosis rate, and cell cycle. The levels of Shrm4, GABAB1, Bcl-2-associated protein x (Bax), B cell lymphoma 2 (Bcl-2), cleaved Caspase-3, microtubule-associated protein 2 (MAP-2) as well as suppressor of cytokine signaling 2 (SOCS2) were detected to further assess the role of Shrm4 and GABA pathway in NSCs. Initially, we found that Shrm4 could bind to GABAB1, and overexpression of Shrm4 or activation of GABAB1 increased the number of positive cells, and promoted cell viability, colony formation rate and differentiation of NSCs. After overexpression of Shrm4 or activation of GABAB1, cells in the G1 phase were decreased, while those in the S phase were increased with an inhibited cell apoptosis rate in the NSCs. Besides, the overexpression of Shrm4 or activation of GABAB1 upregulated the levels of Shrm4, GABAB1, Bcl-2, MAP-2 and SOCS2, while downregulated Bax and cleaved Caspase-3 in NSCs. Overall, overexpression of Shrm4 activated GABAB1 to stimulate the proliferation and differentiation of NSCs. Thus, Shrm4 might be considered as a novel target for promoting the proliferation and differentiation of NSCs.


Assuntos
Diferenciação Celular , Proliferação de Células , Regulação da Expressão Gênica , Proteínas dos Microfilamentos/metabolismo , Células-Tronco Neurais/metabolismo , Transdução de Sinais , Ácido gama-Aminobutírico/metabolismo , Animais , Camundongos , Proteínas dos Microfilamentos/genética , Células-Tronco Neurais/citologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptores de GABA-B/genética , Receptores de GABA-B/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
20.
J Photochem Photobiol B ; 202: 111698, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31734436

RESUMO

Gastric cancer was a foremost one among the majority of regular carcinoma cases globally. Even the achievements on enhanced treatment approaches and early findings cannot decrease the mortality and morbidity ranges of gastric cancer. This current work was planned to develop Morus nigra-loaded zinc oxide nanoparticles (MN-ZnONPs) and to evaluate the different characteristic methods likes UV-vis spectroscopy, TEM, SEM, FT-IR, EDX and XRD. Furthermore, the anticancer effect of MN-ZnONPs against AGS cells were analysed via cell viability, apoptotic morphological variations by AO/EtBr, alterations of mitochondrial membrane potential (MMP), cell cycle arrest, lipid peroxidation status (TBARS), antioxidants (SOD, GSH and CAT) and generation of ROS. Moreover, the status of apoptosis gene such as Bax, caspase-9, caspase-3 and Bcl-2 expressions was analysed by using RT-PCR techniques. We observed the synthesized MN-ZnONPs have a spherical shape, crystalline nature and present different functional groups. We also observed that gastric cancer cells demonstrated in cell death by MN-ZnONPs treatments. The MN-ZnONPs induced apoptosis by enhanced formation of ROS, decreased MMP, apoptotic morphological modifications were evaluated by AO/EtBr, increased lipid peroxidation, decreased antioxidants and induced cell cycle arrest were observed. Furthermore, to confirm the molecular mechanism demonstrated of MN-ZnONPs to induce apoptosis by altering the gene expressions of apoptosis markers were observed.


Assuntos
Antineoplásicos/síntese química , Nanopartículas Metálicas/química , Morus/química , Óxido de Zinco/química , Antineoplásicos/farmacologia , Antioxidantes/química , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 3/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação da Expressão Gênica/efeitos dos fármacos , Química Verde , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Morus/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
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