Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 27
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Environ Toxicol ; 29(7): 740-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-22848001

RESUMO

Chrysophanol (1,8-dihydroxy-3-methylanthraquinone) is one of the anthraquinone compounds, and it has been shown to induce cell death in different types of cancer cells. The effects of chrysophanol on human lung cancer cell death have not been well studied. The purpose of this study is to examine chrysophanol-induced cytotoxic effects and also to investigate such influences that involved apoptosis or necrosis in A549 human lung cancer cells in vitro. Our results indicated that chrysophanol decreased the viable A549 cells in a dose- and time-dependent manner. Chrysophanol also promoted the release of reactive oxygen species (ROS) and Ca(2+) and decreased the levels of mitochondria membrane potential (ΔΨm ) and adenosine triphosphate in A549 cells. Furthermore, chrysophanol triggered DNA damage by using Comet assay and DAPI staining. Importantly, chrysophanol only stimulated the cytocheome c release, but it did not activate other apoptosis-associated protein levels including caspase-3, caspase-8, Apaf-1, and AIF. In conclusion, human lung cancer A549 cells treated with chrysophanol exhibited a cellular pattern associated with necrotic cell death and not apoptosis in vitro. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 740-749, 2014.


Assuntos
Antraquinonas/farmacologia , Antineoplásicos/farmacologia , Neoplasias Pulmonares/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Trifosfato de Adenosina/metabolismo , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Caspase 3/metabolismo , Caspase 8/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Humanos , Neoplasias Pulmonares/metabolismo , Necrose , Estresse Oxidativo/efeitos dos fármacos , Pontos de Checagem da Fase S do Ciclo Celular
2.
Environ Toxicol ; 28(8): 471-8, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21786383

RESUMO

Propofol (2,6-diisopropylphenol) is the most extensively used general anesthetic-sedative agent and it is employed in clinical patients. It has been shown that propofol exhibits anticancer activities. However, there is no available information to address propofol-induced cytotoxic effects and affected gene expressions on murine leukemia cells. Therefore, we investigated the effects of propofol on the levels of protein and gene expression, which are associated with apoptotic death in mouse leukemia RAW 264.7 cells in vitro. Results indicated that propofol induced cell morphological changes, cytotoxicity, and induction of apoptosis in RAW 264.7 cells in vitro. Western blot analysis demonstrated that propofol promoted Fas, cytochrome c, caspase-9 and -3 active form and Bax levels, but inhibited Bcl-xl protein level which led to cell apoptosis. Furthermore, cDNA microarray assay indicated that propofol significantly enhanced 5 gene expressions (Gm4884; Gm10883; Lce1c; Lrg1; and LOC100045878) and significantly suppressed 26 gene expressions (Gm10679; Zfp617; LOC621831; LOC621831; Gm5929; Snord116; Gm3994; LOC380994; Gm5592; LOC380994; Gm4638; LOC280487; Gm4638; Tex24; A530064D06Rik; BC094916; EG668725; Gm189; Hist2h3c2; Gm8020; Snord115; Gm3079; Olfr198; Tdh; Snord115; and Olfr1249). Based on these observations, propofol-altered apoptosis-related proteins might result from induction of apoptotic gene expression and inhibition of cell growth gene expression, which finally led to apoptosis in a mouse leukemia cell line (RAW 264.7) in vitro.


Assuntos
Antineoplásicos/farmacologia , Propofol/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromatina/ultraestrutura , Ensaios de Seleção de Medicamentos Antitumorais , Expressão Gênica , Humanos , Camundongos , Análise de Sequência com Séries de Oligonucleotídeos
3.
Arch Pharm Res ; 35(5): 887-95, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22644856

RESUMO

Liver cancer is the most common form of cancer in Taiwan and it usually responds to chemotherapy. However, patients often have side effects to the chemotherapeutic drugs. Thus new agents are urgently required to treat liver cancer. Chrysophanol, one of the anthraquinone derivatives, was reported to inhibit some human cancer cell growth which may be due to the induction of apoptosis similar to other anthraquinone derivatives though such actions have not been reported. In the present study, we reported that chrysophanol inhibits cell growth in Hep3B liver cancer cells based on the following observations: 1) induc cell morphological changes; 2) decreased percentage of viable cells; 3) induced S phase arrest of cell cycle progression; 4) induced DNA damage as measured by comet assay and DAPI staining. Chrysophanol-induced cell death however, seems to be related to necrotic processes rather than typical apoptosis. Chrysophanol induced reactive oxygen species and Ca(2+) production and decreased mitochondrial membrane potential (ΔΨm) and ATP levels in Hep3B cells. No effects were observed on known protein regulators of apoptosis such as Bax and Bcl-2. Chrysophanol-induced cell death took place independently of caspase-8 and -9. Based on our findings, we propose that chrysophanol reduces cellular ATP levels causing a drop in energy resulting in necrotic-like cell death.


Assuntos
Trifosfato de Adenosina/antagonistas & inibidores , Antraquinonas/toxicidade , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/patologia , Mitocôndrias Hepáticas/patologia , Trifosfato de Adenosina/biossíntese , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Mitocôndrias Hepáticas/metabolismo , Necrose
4.
Environ Toxicol ; 27(6): 332-41, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-20925121

RESUMO

Although there have been advances in the fields of surgery, radiotherapy, and chemotherapy of tongue cancer, the cure rates are still not substantially satisfactory. Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the major pungent ingredient of hot chili pepper and has been reported to have an antitumor effect on many human cancer cell types. The molecular mechanisms of the antitumor effect of capsaicin are not yet completely understood. Herein, we investigated whether capsaicin induces apoptosis in human tongue cancer cells. Capsaicin decreased the percentage of viable cells in a dose-dependent manner in human tongue cancer SCC-4 cells. In addition, capsaicin produced DNA fragmentation, decreased the DNA contents (sub-G1 phase), and induced G0/G1 phase arrest in SCC-4 cells. We demonstrated that capsaicin-induced apoptosis is associated with an increase in reactive oxygen species and Ca²âº generations and a disruption of the mitochondrial transmenbrane potential (ΔΨ(m)). Treatment with capsaicin induced a dramatic increase in caspase-3 and -9 activities, as assessed by flow cytometric methods. A possible mechanism of capsaicin-induced apoptosis is involved in the activation of caspase-3 (one of the apoptosis-executing enzyme). Confocal laser microscope examination also showed that capsaicin induced the releases of AIF, ATF-4, and GADD153 from mitochondria of SCC-4 cells.


Assuntos
Apoptose/efeitos dos fármacos , Capsaicina/farmacologia , Estresse do Retículo Endoplasmático , Mitocôndrias/metabolismo , Neoplasias da Língua/tratamento farmacológico , Cálcio/metabolismo , Capsaicina/uso terapêutico , Caspase 3/metabolismo , Ciclo Celular , Linhagem Celular Tumoral , Fragmentação do DNA/efeitos dos fármacos , Humanos , Espécies Reativas de Oxigênio/metabolismo , Células Tumorais Cultivadas
5.
Int J Urol ; 19(1): 61-70, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22151644

RESUMO

OBJECTIVES: To focus on bee venom-induced apoptosis in human bladder cancer TSGH-8301 cells and to investigate its signaling pathway to ascertain whether intracellular calcium iron (Ca(2+)) is involved in this effect. METHODS: Bee venom-induced cytotoxic effects, productions of reactive oxygen species and Ca(2+) and the level of mitochondrial membrane potential (ΔΨm) were analyzed by flow cytometry. Apoptosis-associated proteins were examined by Western blot analysis and confocal laser microscopy. RESULTS: Bee venom-induced cell morphological changes and decreased cell viability through the induction of apoptosis in TSGH-8301 cell were found. Bee venom promoted the protein levels of Bax, caspase-9, caspase-3 and endonuclease G. The enhancements of endoplasmic reticulum stress-related protein levels were shown in bee venom-provoked apoptosis of TSGH-8301 cells. Bee venom promoted the activities of caspase-3, caspase-8, and caspase-9, increased Ca(2+) release and decreased the level of ΔΨm. Co-localization of immunofluorescence analysis showed the releases of endonuclease G and apoptosis-inducing factor trafficking to nuclei for bee venom-mediated apoptosis. The images revealed evidence of nuclear condensation and formation of apoptotic bodies by 4',6-diamidino-2-phenylindole staining and DNA gel electrophoresis showed the DNA fragmentation in TSGH-8301 cells. CONCLUSIONS: Bee venom treatment induces both caspase-dependent and caspase-independent apoptotic death through intracellular Ca(2+) -modulated intrinsic death pathway in TSGH-8301 cells.


Assuntos
Apoptose/efeitos dos fármacos , Venenos de Abelha/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Neoplasias da Bexiga Urinária , Apoptose/fisiologia , Fator de Indução de Apoptose/metabolismo , Cálcio/metabolismo , Sinalização do Cálcio/fisiologia , Caspase 3/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Endodesoxirribonucleases/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/fisiologia , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Potencial da Membrana Mitocondrial/fisiologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
6.
Cell Biochem Funct ; 29(8): 641-50, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21887696

RESUMO

Curcumin from the rhizome of the Curcuma longa plant has been noted for its chemo-preventative and chemo-therapy activities, and it inhibits the growth of many types of human cancer cell lines. In this study, the mechanisms of cell death involved in curcumin-induced growth inhibition, including cell cycle arrest and induction of apoptosis in human tongue cancer SCC-4 cells, were investigated. Herein, we observed that curcumin inhibited cell growth of SCC-4 cells and induced cell death in a dose-dependent manner. Treatment of SCC-4 cells with curcumin caused a moderate and promoted the G(2) /M phase arrest, which was accompanied with decreases in cyclin B/CDK1 and CDC25C protein levels. Moreover, curcumin significantly induced apoptosis of SCC-4 cells with a decrease of the Bcl-2 level, reduction of mitochondrial membrane potential (ΔΨ(m) ), and promoted the active forms of caspase-3. Curcumin also promoted the releases of AIF and Endo G from the mitochondria in SCC-4 cells by using confocal laser microscope. Therefore, we suggest that curcumin induced apoptosis through a mitochondria-dependent pathway in SCC-4 cells. In addition, we also found that curcumin-induced apoptosis of SCC-4 cells was partly through endoplasmic reticulum stress. In conclusion, curcumin increased G(2) /M phase arrest and induced apoptosis through ER stress and mitochondria-dependent pathways in SCC-4 cells.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/fisiopatologia , Curcumina/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Extratos Vegetais/farmacologia , Neoplasias da Língua/fisiopatologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Caspase 3/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Curcuma/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neoplasias da Língua/tratamento farmacológico , Neoplasias da Língua/metabolismo
7.
Int J Oncol ; 39(2): 319-28, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21617861

RESUMO

Curcumin, a potent candidate anticancer agent, is a dietary pigment (phenolic compound) derived from the food flavoring spice turmeric (Curcuma longa), and it has been shown to have inhibitory effects on tumor cells through anti-proliferative and proapoptotic activities. However, there is no report showing curcumin-induced apoptotic cell death in human nasopharyngeal carcinoma cells in vitro. Thus, this study was performed to elucidate whether mitochondria and caspase cascades are involved in the modulation of apoptosis and cell cycle arrest in curcumin-treated NPC-TW 076 human nasopharyngeal carcinoma cells. The effects of curcumin on cell cycle arrest and apoptosis were measured by flow cytometry, and caspase-3 activity, apoptosis-associated protein levels and its regulated molecules were studied by flow cytometric assay and immunoblots. The results indicated that curcumin-induced G2/M phase arrest was associated with a marked decrease in the protein expression of cyclin A, cyclin B and cyclin-dependent kinase 1 (Cdk1). Curcumin-induced apoptosis was accompanied with upregulation of the protein expression of Bax and downregulation of the protein levels of Bcl-2, resulting in dysfunction of mitochondria and subsequently led to cytochrome c release and sequential activation of caspase-9 and caspase-3 in NPC-TW 076 cells in a time-dependent manner. These findings revealed that mitochondria, AIF caspase-3- dependent pathways play a vital role in curcumin-induced G2/M phase arrest and apoptosis of NPC-TW 076 cells in vitro.


Assuntos
Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Curcumina/farmacologia , Mitocôndrias/metabolismo , Neoplasias Nasofaríngeas/fisiopatologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Acetilcisteína/farmacologia , Antineoplásicos/farmacologia , Cálcio/metabolismo , Carcinoma , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citosol/metabolismo , Dano ao DNA/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Modelos Biológicos , Carcinoma Nasofaríngeo
8.
Hum Exp Toxicol ; 30(8): 1045-52, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20930028

RESUMO

Matrix metalloproteinases (MMPs) play an important role in the invasion, metastasis and angiogenesis of cancer cells. Many agents have been shown to inhibit the cancer cell migration and invasion by suppression of MMPs. 2-(3-Methoxyphenyl)-6,7-methylenedioxoquinolin-4-one (MMEQ) is a derivative compound synthesized from quinolin and the purpose of this study is to determine whether or not cell migration would be reduced in human bladder cancer TSGH8301 cells after MMEQ treatment. Wound healing assay and boyden chamber assay were used in cell migration and invasion determinations. Cell migration and invasion inhibited by MMEQ exerted an inhibitory effect on the sevenless homolog-1 (SOS-1), protein kinase c (PKC), extracellular signal-regulated kinase (ERK) and Rho A for causing the inhibitions of MMP-2 and -9, and then followed by the inhibitions of invasion and migration. MMEQ also affected FAK, PI3K or inhibited growth factor receptor-bound protein 2 (GRB2), nuclear factor kappaB (NF-κB), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) for cell proliferation inhibition. Therefore, MMEQ may serve as a drug in the prevention of tumor metastasis of bladder cancer in the future.


Assuntos
Antineoplásicos/farmacologia , Benzodioxóis/farmacologia , Movimento Celular/efeitos dos fármacos , Quinolonas/farmacologia , Antineoplásicos/química , Benzodioxóis/química , Western Blotting , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Inibidores de Metaloproteinases de Matriz , Estrutura Molecular , Invasividade Neoplásica , Metástase Neoplásica , Quinolonas/química
9.
Hum Exp Toxicol ; 30(8): 1053-61, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20937639

RESUMO

Apigenin (4,5,7-trihydroxyflavone), a promising chemopreventive agent presented in fruits and vegetables, has been shown to induce cell cycle arrest and apoptosis in many types of human cancer cell lines. However, there is no available information to address the effects of apigenin on human lung cancer H460 cells. In the present studies, H460 cells were treated with apigenin for different time and then were analyzed for the morphological changes, induction of apoptosis, protein levels associated with apoptosis and results in dose-dependent induction of morphological changes, decrease in the percentage of viability, induced DNA damage and apoptosis; down-modulation of the protein expression of Bid, Bcl-2, procaspase-8; up-regulation of protein levels of Bax, caspase-3, AIF, cytochrome c, GRP78 and GADD153; decreased the levels of mitochondrial membrane potential and increased the productions of reactive oxygen species (ROS) and Ca(2+) in H460 cells. Taken together, this is the first systematic in vitro study showing the involvement of apoptosis regulatory proteins as potential molecular targets of apigenin in human lung cancer H460 cells.


Assuntos
Anticarcinógenos/farmacologia , Apigenina/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/biossíntese , Cálcio/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromatina/metabolismo , Relação Dose-Resposta a Droga , Chaperona BiP do Retículo Endoplasmático , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima
10.
J Agric Food Chem ; 58(20): 11148-55, 2010 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-20863062

RESUMO

Phenethyl isothiocyanate (PEITC), one of the major compounds from dietary cruciferous vegetables, has been found to have antitumor properties and therefore could generate special interest for the development of chemopreventive and/or chemotherapeutic agent for human cancers. In the primary studies, we found that PEITC induced cytotoxic effect (decreased the percentage of viable cells) in human colon cancer HT29 cells. Here, in this study, we are the first to report the antimetastatic effect of PEITC in HT29 human colon cancer cells. The results show that PEITC exhibited an inhibitory effect on the abilities of adhesion, migration, and invasion by Boyden chamber assay. Western blotting examination indicated that PEITC exerted an inhibitory effect on the SOS-1, PKC, ERK1/2 and Rho A for causing the inhibitions of MMP-2 and -9 then followed by the inhibition of invasion and migration of HT29 cells in vitro. PEITC also affected Ras, FAK, PI3K or inhibited GRB2, NF-κB, iNOS and COX-2 for causing the inhibition of cell proliferation in HT29 cells. Real-time PCR also showed that PEITC inhibited the gene expressions of MMP-2, -7, -9, FAK and Rho A after PEITC treatment for 48 h in HT29 cells. PEITC also inhibited the activities of AKT, ERK, JNK and PKC. Our results provide a new insight into the mechanisms and functions of PEITC which inhibit migration and invasion of HT29 human colon cancer cells. These results suggest that molecular targeting of NF-κB led to the inhibition of MMP-2, -7, and -9 and it might be a useful strategy for the inhibition of migration and invasion on human colon cancer.


Assuntos
Antineoplásicos/farmacologia , Neoplasias do Colo/fisiopatologia , Isotiocianatos/farmacologia , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Verduras/química , Movimento Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Regulação para Baixo/efeitos dos fármacos , Células HT29 , Humanos , Invasividade Neoplásica
11.
Arch Pharm Res ; 33(8): 1181-91, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20803121

RESUMO

Dietary polyphenols have been correlated with a reduced risk of developing cancer. Quercetin (a natural polyphenolic compound) induced apoptosis in many human cancer cell lines, including breast cancer MCF-7 cells. However, the involvement of possible signaling pathways and the roles of quercetin in apoptosis are still undefined. The purpose of this study was to investigate the effects of quercetin on the induction of the apoptotic pathway in human breast cancer MCF-7 cells. When MCF-7 cells were treated with quercetin for 24 and 48 h and at various doses (10-175 microM), cell viability decreased significantly in time- and dose-dependent manners. Exposure of MCF-7 cells to 10-175 microM quercetin resulted in an approximate 90.25% decrease in viable cells. To explicate the mechanism underlying the antiproliferative effect of quercetin, cell cycle distribution and apoptosis in MCF-7 cells was investigated after exposure to 150 microM quercetin for 6-48 h. Quercetin caused a remarkable increase in the number of S phase (14.56% to 61.35%) and sub-G1 phase cells (0.1% to 8.32%) in a dose- and time-dependent manner. Quercetin caused S phase arrest by decreasing the protein expression of CDK2, cyclins A and B while increasing the p53 and p57 proteins. Following incubation with quercetin for 48 h, MCF-7 cells showed apoptotic cell death by the decreased levels of Bcl-2 protein and DeltaPsi(m) and increased activations of caspase-6, -8 and -9. Moreover, quercetin increased the AIF protein released from mitochondria to nuclei and the GADD153 protein translocation from endoplasmic reticulum to the nuclei. These data suggested that quercetin may induce apoptosis by direct activation of the caspase cascade through the mitochondrial pathway in MCF-7 cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Quercetina/farmacologia , Antineoplásicos Fitogênicos/administração & dosagem , Fator de Indução de Apoptose/efeitos dos fármacos , Fator de Indução de Apoptose/metabolismo , Neoplasias da Mama/patologia , Caspases/efeitos dos fármacos , Caspases/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Relação Dose-Resposta a Droga , Feminino , Humanos , Mitocôndrias/efeitos dos fármacos , Quercetina/administração & dosagem , Fatores de Tempo , Fator de Transcrição CHOP/efeitos dos fármacos , Fator de Transcrição CHOP/metabolismo
12.
Int J Oncol ; 36(6): 1477-84, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20428772

RESUMO

The molecular mechanism and possible signaling pathway of apigenin-induced cytotoxicity and apoptosis in human lung cancer cells has not been reported. We investigated the role of ROS, Ca2+, caspases and Bax proteins and mitochondria membrane potential in apigenin-induced apoptosis in A549 cells. Cells were incubated with different concentrations of apigenin then cell morphological changes, DNA damage, cell viability and apoptosis were determined by Comet assay, and flow cytometric analysis. Sub-G1 phase was also examined. Western blot analysis was used to determined the levels of Bax and Bcl-2 and apoptosis associated proteins, and confocal laser microscope for examining the translocation of associated protein after exposed to apigenin. The results indicated that apigenin induced morphological changes, decreased percentage of viable cells and induced apoptosis dose- and time-dependently. DAPI staining and Comet assay also confirmed that apigenin-induced DNA condensation and damage. The levels of caspase-3, -8 and -9 involved in apigenin-induced apoptosis indicating caspase-dependent pathway was induced by apigenin. Western blotting showed that apigenin promoted cytochrome c levels and also induced dysfunction of mitochondria leading to the release of cytochrome c, AIF and Endo G, causing the activation of caspase-9 and -3, then apoptosis in A549 cells.


Assuntos
Antineoplásicos/farmacologia , Apigenina/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Pulmonares/metabolismo , Mitocôndrias/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Western Blotting , Caspases/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Separação Celular , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Citometria de Fluxo , Humanos , Neoplasias Pulmonares/patologia , Microscopia Confocal , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Proteína X Associada a bcl-2/efeitos dos fármacos
13.
Hum Exp Toxicol ; 29(5): 359-67, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20197453

RESUMO

Solanum lyratum Thunberg (Solanaceae) has been used as a folk medicine for treating liver, lung and esophagus in the Chinese population. Our previous studies have shown that the crude extract of S. lyratum Thunberg (SLE) induced apoptosis in colo 205 human colon adenocarcinoma cells; however, there is no report to show SLE affect immune responses in vivo. In this study, the in vivo effects of SLE on leukemia WEHI-3 cells and immune responses such as phagocytosis and natural killer (NK) cell activity in normal and leukemia mice were investigated. The SLE treatment decreases surface markers of CD3 and Mac-3 in normal and leukemia mice but promoted the cell markers of CD19 and CD11b in normal mice and CD11b in leukemia mice indicating that the precursors of T cells was inhibited and B cells and macrophage were promoted. The SLE treatment promoted the activity of macrophage phagocytosis in the peripheral blood mononuclear cells (PBMC) and peritoneal cells from normal and leukemia mice. The results also showed that NK cells from the normal and leukemia mice after treatment with SLE can kill the YAC-1 target cells. Therefore, the SLE treatment increased macrophage and NK cell activities. These consistent results indicate SLE could be a potent immune responses agent.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Leucemia Experimental/tratamento farmacológico , Extratos Vegetais/farmacologia , Solanum/química , Animais , Antígenos de Diferenciação/metabolismo , Linfócitos B/efeitos dos fármacos , Complexo CD3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Matadoras Naturais/efeitos dos fármacos , Leucemia Experimental/imunologia , Leucemia Experimental/patologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/fisiologia , Ativação Linfocitária/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Fagocitose/efeitos dos fármacos , Fagocitose/fisiologia , Fitoterapia , Baço/efeitos dos fármacos , Baço/patologia , Linfócitos T/efeitos dos fármacos
14.
Oncol Rep ; 23(3): 665-70, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20127004

RESUMO

Cancer metastasis involves multiple processes which may complicate clinical management and even lead to death. Matrix metalloproteinases (MMPs) play an important role in cancer cell invasion, metastasis and angiogenesis, depending on whether agents can inhibit MMPs which could lead to inhibition of the migration and invasion of cancer cells. Curcumin, the active constituent of the dietary spice turmeric, has potential for the prevention and therapy of cancer. However, there is no study to address the effects of curcumin on migration and invasion of mouse-rat hybrid retina ganglion cells (N18). This is the first study to explore the anti-migration and -invasion of curcumin in mouse-rat hybrid retina ganglion cells (N18) in vitro. Curcumin exerted a dose- and time-dependent inhibitory effect on the invasion and migration of N18 cells in vitro. Results from Western blotting showed that curcumin inhibited the protein levels of PKC, FAK, NF-kappaB p65 and Rho A leading to the inhibition of ERK1/2, MKK7, COX-2 and ROCK1, respectively, finally causing the inhibition of MMP-2 and -9 for the inhibition of migration and invasion of N18 cells. Moreover, this action was involved in the inhibition of gene expression of MMP-2 and -7, FAK, ROCK1 and Rho A. Overall, the above data show that the anticancer effect of curcumin also exists for the inhibition of migration and invasion in N18 cells, and that curcumin may be a powerful candidate for developing preventive agents for cancer metastasis.


Assuntos
Antineoplásicos/farmacologia , Curcumina/farmacologia , Proteína-Tirosina Quinases de Adesão Focal/antagonistas & inibidores , Linfoma/patologia , Inibidores de Metaloproteinases de Matriz , Células Ganglionares da Retina/efeitos dos fármacos , Quinases Associadas a rho/antagonistas & inibidores , Proteína rhoA de Ligação ao GTP/antagonistas & inibidores , Animais , Movimento Celular , Proteína-Tirosina Quinases de Adesão Focal/genética , Células Híbridas , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Camundongos , Invasividade Neoplásica , RNA Mensageiro/análise , Ratos , Células Ganglionares da Retina/fisiologia , Quinases Associadas a rho/genética , Proteína rhoA de Ligação ao GTP/genética
15.
Anticancer Res ; 29(10): 4063-70, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19846952

RESUMO

Many phytochemicals have been recognized to have potential chemopreventive or chemotherapeutic efficacy in cancer treatment. In this study, we hypothesized that berberine would have anticancer activities in SCC-4 human tongue cancer cells. Results indicated that berberine reduced the viability of SCC-4 cells, which was initiated by the generation of reactive oxygen species, via an increase in cytosolic Ca(2+). Berberine-induced apoptosis was associated with a reduction of the mitochondrial membrane potential associated with changes in the Bax/Bcl-2 ratio, release of cytochrome c from mitochondria and activation of down stream caspase-3. Real-time PCR showed that berberine stimulated gene expression of caspase-8, -9 and -3, apoptosis-inducing factor and endonuclease G. The present study demonstrated that berberine-mediated apoptosis of SCC-4 cells is regulated by ROS, mitochondria, caspase-3-dependent and mitochondria-dependent pathways, suggesting that berberine may be considered for future studies as a promising therapeutic candidate for human tongue cancer.


Assuntos
Fator de Indução de Apoptose/biossíntese , Apoptose/efeitos dos fármacos , Berberina/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Caspases/biossíntese , Endodesoxirribonucleases/biossíntese , Neoplasias da Língua/tratamento farmacológico , Neoplasias da Língua/metabolismo , Fator de Indução de Apoptose/genética , Cálcio/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Caspases/genética , Linhagem Celular Tumoral , Citosol/metabolismo , Dano ao DNA , Endodesoxirribonucleases/genética , Citometria de Fluxo , Humanos , Isoenzimas , Potencial da Membrana Mitocondrial/efeitos dos fármacos , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Espécies Reativas de Oxigênio/metabolismo , Neoplasias da Língua/genética , Neoplasias da Língua/patologia
16.
Hum Exp Toxicol ; 28(12): 785-90, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19850653

RESUMO

It is well documented that enhanced garlic (Allium sativum) consumption leads to decrease in the cancer incidences. Diallyl sulfide (DAS), one of the components of garlic, induces cytotoxicity and apoptosis in many cancer cell lines. The present studies are focused on the in vivo effects of DAS on leukemia WEHI-3 cells in the BALB/c mice. We examined the effects of DAS on the cytotoxicity of WEHI-3 cells and results indicated that DAS decreased the percentage of viable WEHI-3 cells and these effects are dose-dependent. We examined the effects of DAS on WEHI-3 in vivo and the results indicated that DAS decreased the percentage of Mac-3 and CD11b, indicating that the differentiation of the precursor of macrophage cells was inhibited. DAS stimulated the percentage of CD3 and CD19, indicating that the differentiation of the precursor of T and B cells promoted. The weights of liver and spleen indicated that DAS decreased the weight of these organs after being compared to the control groups. One of the major characteristic of WEHI-3 leukemia is the enlarged spleen in murine after intraperitoneal (i.p.) injection of WEHI-3 cells. In conclusion, DAS affects WEHI-3 cells both in vitro and in vivo.


Assuntos
Compostos Alílicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Leucemia/tratamento farmacológico , Sulfetos/farmacologia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Corantes , Relação Dose-Resposta a Droga , Imunofluorescência , Indicadores e Reagentes , Leucemia/patologia , Fígado/patologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Baço/patologia , Sais de Tetrazólio , Tiazóis
17.
Oncol Rep ; 22(5): 1033-7, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19787217

RESUMO

In this study, we investigated the effect of danthron on the cell migration and invasion of human brain glioblastoma multiforme GBM 8401 cells in vitro. The changes of migration and invasion of GBM 8401 cells after treatment with danthron were detected by cell migration assay and cell invasion assay. The levels of mRNA gene expression associated with cell migration and invasion were detected by real-time PCR. Results indicated that human brain glioblastoma multiforme GBM 8401 cells treated with danthron in vitro migrated and invaded less than cells treated with phosphate-buffered saline (PBS) (control). Western blotting showed that danthron inhibited the protein levels of FAK, MMP-7, MMP-9 and uPA in GBM 8401 cells. Real-time PCR assay also showed that danthron inhibited the mRNA expression of matrix metalloproteinase-9 (MMP-9), FAK and ROCK-1 of GBM 8401 cells. These results showed that danthron inhibited invasion and migration of GBM 8401 cells by downregulating mRNA expression associated with these processes, resulting in reduced metastasis. Thus, danthron may be considered a therapeutic agent that can inhibit primary tumor growth and prevent metastasis.


Assuntos
Antraquinonas/farmacologia , Movimento Celular/efeitos dos fármacos , Quinase 1 de Adesão Focal/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Metaloproteinase 9 da Matriz/genética , Quinases Associadas a rho/genética , Western Blotting , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Adesão Celular/efeitos dos fármacos , Quinase 1 de Adesão Focal/metabolismo , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Mutagênicos/farmacologia , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Quinases Associadas a rho/metabolismo
18.
Food Chem Toxicol ; 47(1): 171-9, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19038304

RESUMO

In this study, we investigated the effects of DADS on human colon cancer cell line COLO 205 on cell cycle arrest and apoptosis in vitro. After 24 h treatment of COLO 205 cells with DADS, the dose- and time-dependent decreases of viable cells were observed and the IC50 was 22.47 microM. The decreased percentages of viable cells are associated with the production of ROS. Treatment of COLO 205 cells with DADS resulted in G2/M phase arrest and apoptosis occurrence through the mitochondrial-pathway (Bcl-2, Bcl-xL down-regulation and Bak, Bax up-regulation). DADS increased cyclin B, cdc25c-ser-216-9 and Wee1 but did not affect CDK1 protein and gene expression within 24 h of treatment. DADS-induced apoptosis was examined and confirmed by DAPI staining and DNA fragmentation assay. DADS promoted caspase-3, -8 and -9 activity and induced apoptosis were accompanied by increasing the levels of Fas, phospho-Ask1 and -JNK, p53 and decreasing the mitochondrial membrane potential which then led to release the cytochrome c, cleavage of pro-caspase-9 and -3. The COLO 205 cells were pre-treated with JNK inhibitor before leading to decrease the percentage of apoptosis which was induced by DADS. Inhibition of caspase-3 activation blocked DADS-induced apoptosis on COLO 205 cells.


Assuntos
Compostos Alílicos/farmacologia , Caspases/metabolismo , Neoplasias do Colo/tratamento farmacológico , Dissulfetos/farmacologia , Retículo Endoplasmático/efeitos dos fármacos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos
19.
Anticancer Res ; 28(3A): 1701-11, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18630529

RESUMO

Baicalein was investigated for tumor cell-specific cytotoxicity, apoptosis-inducing activity and signal pathway against the MDA-MB-231 human breast cancer cell line. After the MDA-MB-231 cells had been treated with baicalein, trypan blue exclusion, propidium iodide (PI) assay and 4',6-diamidino-2-phenylindole (DAPI) were used to stain the dead cells and detect apoptosis, respectively. The effects of baicalein on the levels of reactive oxygen species (ROS), Ca2+ and mitochondrial membrane potential (deltapsim) on MDA-MB-231 cells were examined by flow cytometric assays. The ROS caused endoplasmic reticulum (ER) stress, confirmed by the increase of GADD153 and GRP78 in the examined cells. GADD153 and GRP78 increases were also confirmed by confocal laser microscopy examination and indicated that both proteins translocated to the nucleus. The effects of baicalein on the expression of apoptotic-regulated genes, such as Bcl-2 family and caspase, were detected by Western blotting. To further investigate the apoptotic pathway and the role of Ca2+ induced by baicalein, a caspase-3 inhibitor and Ca2+ chelator were used to block caspase-3 activity and Ca2+ in MDA-MB-231 cells. Baicalein induced apoptosis in a time-dependent effect through the inhibition of Bcl-2 expression, increased the levels of Bax, reduced the level of deltapsim, and promoted the cytochrome c release and caspase-3 activation. MDA-MB-231 cells were pretreated with BAPTA which reduced the levels of Ca2+, deltapsim and apoptosis. In conclusion, baicalein induced apoptosis via Ca2+ production, mitochondria-dependent and caspase-3 activation in MDA-MB-231 cells.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Cálcio/metabolismo , Caspase 3/metabolismo , Flavanonas/farmacologia , Mitocôndrias/efeitos dos fármacos , Apoptose/fisiologia , Western Blotting , Neoplasias da Mama/prevenção & controle , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/fisiologia , Linhagem Celular Tumoral , Citocromos c/biossíntese , Ácido Egtázico/análogos & derivados , Ácido Egtázico/farmacologia , Chaperona BiP do Retículo Endoplasmático , Citometria de Fluxo , Proteínas de Choque Térmico/biossíntese , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Microscopia de Fluorescência , Mitocôndrias/fisiologia , Chaperonas Moleculares/biossíntese , Oligopeptídeos/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição CHOP/biossíntese , Fator de Transcrição CHOP/genética , Proteína X Associada a bcl-2/biossíntese
20.
Anticancer Res ; 28(2A): 833-42, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18507026

RESUMO

Although it has been previously reported that bee venom (BV) can induce apoptosis in many cancer cell lines, there is no information on the effect of BV on human cervical cancer cells and its molecular mechanisms of action are not fully elucidated. In this study, the possible mechanisms of apoptosis by which BV acts on human cervical cancer Ca Ski cells were investigated. BV induced morphological changes and decreased the percentage of viable Ca Ski cells in a dose- and time-dependent manner. Flow cytometric analysis demonstrated that BV induced the production of reactive oxygen species, increased the level of cytoplasmic Ca2+, reduced mitochondrial membrane potential which led to cytochrome c release, and promoted the activation of caspase-3 which then led to apoptosis. BV also induced an increase in the levels of Fas, p53, p21 and Bax, but a decrease in the level of Bcl-2. The activities of both caspase-8 and caspase-9 were enhanced by BV, promoting caspase-3 activation, leading to DNA fragmentation. Based on the DNA fragmentation and DAPI staining, BV-induced apoptosis was mitochondrial-dependent and caspase-dependent. BV also promoted the expression of AIF and Endo G in the Ca Ski cells. Both AIF and Endo G proteins were released from the mitochondria, and then induced apoptosis which was not through activation of caspase. In conclusion, our data demonstrated that BV-induced apoptosis occurs via a Fas receptor pathway involving mitochondrial-dependent pathways and is closely related to the level of cytoplasmic Ca2+ in Ca Ski cells.


Assuntos
Apoptose/efeitos dos fármacos , Venenos de Abelha/farmacologia , Ciclo Celular/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Neoplasias do Colo do Útero/tratamento farmacológico , Cálcio/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Espécies Reativas de Oxigênio , Neoplasias do Colo do Útero/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...