RESUMEN
Pancreatic cancer is aggressive and therefore difficult to treat; however, continued efforts have been made with the aim of developing an effective therapy against the disease. The Hedgehog (Hh) signaling pathway is reportedly involved in the proliferation and survival of pancreatic cancer cells. The transcription factor glioma-associated oncogene (Gli) is a key component of the Hh signaling pathway and the primary effector of pancreatic cancer development. Inhibiting Gli is a proven therapeutic strategy for this disease. The present study examined the regulation of Gli and the expression of its target genes to identify an inhibitor of the Sonic Hh (Shh) pathway. A germacranolide sesquiterpene lactone (GSL) was isolated from Siegesbeckia glabrescens as an inhibitor of Gli-mediated transcription. The results demonstrated that GSL inhibited Shh-induced osteoblast differentiation and Gli homolog 1 (Gli1)-mediated transcriptional activity in mesenchymal C3H10T1/2 stem cells. Furthermore, GSL suppressed Gli-mediated transcriptional activity in human pancreatic cancer PANC-1 and AsPC-1 cells, which resulted in reduced cancer cell proliferation and downregulated expression of the Gli-target genes, Gli1 and cyclin D1. A sesquiterpene lactone from S. glabrescens may therefore serve as a candidate for the treatment of Hh/Gli-dependent pancreatic cancer.
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BACKGROUND: Black ginseng (Ginseng Radix nigra, BG) refers to the ginseng steamed for nine times and fine roots (hairy roots) of that is called fine black ginseng (FBG). It is known that the content of saponin of FBG is higher than that of BG. Therefore, in this study, we examined antitumor effects against MCF-7 breast cancer cells to target the FBG extract and its main component, ginsenoside Rg5 (Rg5). METHODS: Action mechanism was determined by MTT assay, cell cycle assay and western blot analysis. RESULTS: The results from MTT assay showed that MCF-7 cell proliferation was inhibited by Rg5 treatment for 24, 48 and 72 h in a dose-dependent manner. Rg5 at different concentrations (0, 25, 50 and 100 µM), induced cell cycle arrest in G0/G1 phase through regulation of cell cycle-related proteins in MCF-7 cells. As shown in the results from western blot analysis, Rg5 increased expression of p53, p21(WAF1/CIP1) and p15(INK4B) and decreased expression of Cyclin D1, Cyclin E2 and CDK4. Expression of apoptosis-related proteins including Bax, PARP and Cytochrome c was also regulated by Rg5. These results indicate that Rg5 stimulated cell apoptosis and cell cycle arrest at G0/G1 phase via regulation of cell cycle-associated proteins in MCF-7 cells. CONCLUSION: Rg5 promotes breast cancer cell apoptosis in a multi-path manner with higher potency compared to 20(S)-ginsenoside Rg3 (Rg3) in MCF-7 (HER2-/ER+) and MDA-MB-453 (HER2+/ER-) human breast cancer cell lines, and this suggests that Rg5 might be an effective natural new material in improving breast cancer.
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Homozygous deletion is a frequent mutational mechanism of silencing tumor suppressor genes in cancer. Therefore, homozygous deletions have been analyzed for identification of tumor suppressor genes that can be utilized as biomarkers or therapeutic targets for cancer treatment. In this study, to elucidate potential tumor suppressor genes involved in gastric cancer (GC), we analyzed the entire set of large homozygous deletions in six human GC cell lines through genome- and transcriptome-wide approaches. We identified 51 genes in homozygous deletion regions of chromosomes and confirmed the deletion frequency in tumor tissues of 219 GC patients from The Cancer Genome Atlas database. We evaluated the effect of homozygous deletions on the mRNA level and found significantly affected genes in chromosome bands 9p21, 3p22, 5p14, and 6q15. Among the genes in 9p21, we investigated the potential tumor suppressive effect of KLHL9. We demonstrated that ectopic expression of KLHL9 inhibited cell proliferation and tumor formation in KLHL9-deficient SNU-16 cell line. In addition, we observed that homozygous focal deletions generated truncated transcripts of TGFBR2, CTNNA1, and STXBP5. Ectopic expression of two kinds of TGFBR2-reverse GADL1 fusion genes suppressed TGF-ß signaling, which may lead to the loss of sensitivity to TGF-ß tumor suppressive activity. In conclusion, our findings suggest that novel tumor suppressor genes that are aberrantly expressed through homozygous deletions may play important roles in gastric tumorigenesis.
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Deleción Cromosómica , Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor , Neoplasias Gástricas/genética , Animales , Línea Celular Tumoral , Cromosomas Humanos Par 3 , Cromosomas Humanos Par 5 , Cromosomas Humanos Par 6 , Cromosomas Humanos Par 9 , Femenino , Humanos , Ratones , Ratones Desnudos , Proteínas Serina-Treonina Quinasas/genética , ARN Mensajero/metabolismo , Receptor Tipo II de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/genéticaRESUMEN
BACKGROUND/AIM: The present study aimed to investigate anticancer properties of equol and demonstrate its underlying mechanisms of action in human cervical cancer HeLa cells. MATERIALS AND METHODS: Inhibition of cell viability was examined by 3-(4,5-dimethylthiazoly-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was evaluated by observation of apoptotic cell morphology, and an increase of annexin-V(+) cells. Western blotting was used to examine apoptosis-related proteins. Flow cytometry was used to measure mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). RESULTS: Equol treatment inhibited HeLa cell proliferation in dose- and time-dependent manner. Equol-induced apoptotic cell death was accompanied by the activation of caspases, and alteration of MMP and mitochondrial membrane proteins; equol also rapidly triggered ROS production. Pre-treatment with N-acetylcysteine blocked loss of MMP, caused increase of Bcl-2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2) ratio, caspase-8 activation, and apoptosis induced by equol. CONCLUSION: Equol is a potential anticancer agent against HeLa, with possible mechanisms involved in ROS generation and mitochondrial membrane alteration.
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Apoptosis/efectos de los fármacos , Equol/farmacología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Caspasas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Células HeLa , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Neoplasias del Cuello Uterino/patologíaRESUMEN
Caffeic acid phenethyl ester (CAPE), a phenolic compound derived from honeybee propolis, has been reported to possess anticancer activities in several types of malignant cells. Here, we show that treatment with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in combination with CAPE significantly sensitized SK-Hep1 cells to TRAIL-induced apoptosis. The sensitization to TRAIL was accompanied by the activation of extrinsic and intrinsic apoptotic pathways, leading to the activation of caspases, mitochondrial disruption and PARP cleavage. Moreover, TRAIL receptors, such as DR4 and DR5 were significantly upregulated by CAPE treatment, and both DR4/Fc and DR5/Fc chimera markedly abrogated apoptosis induced by CAPE and TRAIL, demonstrating the critical role of these death receptors in combination-induced apoptosis. The effect of CAPE on mitogen-activated protein kinases (MAPKs) was further examined, where CAPE treatment resulted in the activation of p38 and the inhibition of JNK, without affecting levels of phospho-ERK. Our results showed that p38 and JNK exhibited the opposite role in SK-Hep1 cells. The inhibition of p38, using SB203580, blocked the CAPE-induced expression of death receptors and attenuated the combinationinduced apoptosis, suggesting the pro-apoptotic role of p38. In contrast, JNK-specific inhibition, by SP600125, triggered upregulation of DR4 and DR5, and sensitized SK-Hep1 cells to TRAIL, indicating that the CAPE-induced suppression of JNK may contribute to the sensitizing effect of CAPE through the upregulation of death receptors. Taken together, these results indicate that CAPE potentiated TRAIL-induced apoptosis in SK-Hep1 cells, through upregulation of TRAIL receptors via modulation of p38 and JNK signaling pathways.
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Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , MAP Quinasa Quinasa 4/genética , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/biosíntesis , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Abejas/química , Ácidos Cafeicos/administración & dosificación , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , MAP Quinasa Quinasa 4/biosíntesis , Alcohol Feniletílico/administración & dosificación , Alcohol Feniletílico/análogos & derivados , Própolis/administración & dosificación , Própolis/química , Transducción de Señal/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/biosíntesisRESUMEN
BACKGROUND/AIM: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer therapy due to its selective ability to induce apoptosis of cancer cells. However, some cancer cells are resistant to TRAIL. Here, we demonstrated that treatment with TRAIL, in combination with equol, sensitizes TRAIL-mediated apoptosis of HeLa cells. MATERIALS AND METHODS: Cell viability was evaluated by the colorimetric cell viability assay (MTT). Apoptotic cell death was analyzed by flow cytometry and microscopy. Western blotting was performed to examine protein expression and cell surface expression was evaluated by flow cytometry. Enzymatic activity of caspases was measured by the colorimetric assay. RESULTS: Equol enhanced TRAIL-induced apoptosis through activation of caspase-3, -8, -9, and cleavage of BID. Furthermore, DR4/Fc chimera protein and DR5/Fc chimera protein efficiently reduced the activation of caspases and BID cleavage, as well as apoptotic cell death induced by co-treatment with equol and TRAIL. CONCLUSION: Equol enhances TRAIL-induced apoptosis of HeLa cells through a death receptor-mediated caspase pathway.
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Equol/farmacología , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Apoptosis/efectos de los fármacos , Caspasas/fisiología , Células HeLa , Humanos , Receptores de Muerte Celular/fisiologíaRESUMEN
Taurine is a nonessential amino acid and has a variety of physiological and pharmacological effects. Recently, protective effects of taurine against anticancer drugs on normal cells were investigated. But anticancer effects of taurine on cancer cells remain poorly understood. Therefore, we investigated the anticancer effects of taurine alone and combination of cisplatin with taurine in human cervical cancer cells. Single treatment of taurine decreased cell proliferation in a time- and dose-dependent manner. In co-treatment of cisplatin with taurine, cell proliferation was more decreased than single treatment of cisplatin. Reduced cell proliferation was caused by apoptosis induction. Thus, after treatment of cisplatin with taurine, apoptotic cells were investigated. Apoptotic cells were increased more than taurine or cisplatin alone. Induction of apoptosis was related to p53 expression and activation of caspase-3, caspase-6, caspase-7, and caspase-9. In present study, the results indicated that co-treatment of cisplatin with taurine was more effective than single treatment of cisplatin.
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Antineoplásicos/farmacología , Cisplatino/farmacología , Taurina/farmacología , Neoplasias del Cuello Uterino/patología , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Caspasas/metabolismo , Proliferación Celular/efectos de los fármacos , Cisplatino/uso terapéutico , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Femenino , Células HeLa , Humanos , Poli(ADP-Ribosa) Polimerasas/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/enzimologíaRESUMEN
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is regarded as a promising candidate for anticancer therapy due to its selective toxicity to cancer cells. Nevertheless, because of TRAIL resistance in some cancer cells, combined treatment with sensitizing agents is required to enhance the anticancer potential of TRAIL. In this study, we investigated the underlying mechanism of apigenin-induced sensitization of HepG2 cells to TRAIL-induced cell death. Synergistic induction of apoptosis by combination was confirmed by examining the typical morphology changes of apoptosis, PARP-cleavage, and activation of effector caspases. Z-VAD-fmk, a pan-caspase inhibitor, inhibited the enhanced cell death by combined treatment of apigenin and TRAIL, demonstrating that a caspase-dependent pathway is involved in apigenin/TRAIL-mediated apoptosis. In addition, we found that apigenin/ TRAIL co-treatment up-regulates DR5 cell surface expression. The synergistic induction of cell death by the apigenin/ TRAIL combination was significantly attenuated by DR5 blocking chimera antibody. Next, using pharmacological inhibitors, we found that ERK activation is involved in the induction of DR5 expression. Inhibition of ERK1/2 by U0126 significantly decreased the apigenin/TRAIL-induced DR5 expression and apoptosis. Taken together, our results indicate that apigenin can enhance the apoptotic effect of TRAIL via ERK-induced up-regulation of DR5.
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Apigenina/farmacología , Apoptosis/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Western Blotting , Butadienos/farmacología , Caspasas/metabolismo , Proliferación Celular , Células Hep G2 , Humanos , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 3 Activada por Mitógenos/antagonistas & inhibidores , Nitrilos/farmacología , Poli(ADP-Ribosa) Polimerasas/metabolismoRESUMEN
Platycodin D (PD), a natural compound found in Platycodon grandiflorum, induces apoptotic cell death in various carcinoma cells. One mechanism of PD-mediated cell death is by activation of mitogen-activated protein kinases, as suggested in a recent report. In this study, we further examined upstream signal pathways and the relationship between these signals and reactive oxygen species (ROS). Using immunoblotting assays, we found that PD activated apoptosis signal-regulating kinase 1 (ASK1) through phosphorylation of ASK1 at threonine and dephosphorylation of ASK1 at serine. We also showed that PD caused activation of the endoplasmic reticulum (ER) stress response. This was supported by observations showing that treatment with PD induces phosphorylation of PKR-like ER kinase (PERK) and eukaryotic initiation factor 2 α (eIF 2α), up-regulating expression of glucose-regulated protein 78/immunoglobulin heavy chain binding protein (GRP78/Bip) and CCAAT/enhancer-binding protein homologous protein/growth arrest and DNA damage-inducible gene 153 (CHOP/GADD153) and activation of caspase-4. Furthermore, PD-induced ASK1 and ER stress responses were inhibited by the antioxidant N-acetyl-l-cysteine. These results suggest that ROS play a critical role for activation of ASK1 and ER stress in PD-treated cancer cells.
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Neoplasias de la Mama/enzimología , Estrés del Retículo Endoplásmico , MAP Quinasa Quinasa Quinasa 5/metabolismo , Extractos Vegetales/farmacología , Platycodon/química , Especies Reactivas de Oxígeno/metabolismo , Saponinas/farmacología , Triterpenos/farmacología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Chaperón BiP del Retículo Endoplásmico , Activación Enzimática , Femenino , Humanos , MAP Quinasa Quinasa Quinasa 5/genética , Proteínas Quinasas Activadas por Mitógenos/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Transducción de SeñalRESUMEN
Korean pear (Pyrus pyrifolia cv. Shingo) has been used as a traditional medicine for alleviating alcohol hangover. However, scientific evidence for its effectiveness or mechanism is not clearly established. To investigate its mechanism of alcohol detoxification, both in vitro and in vivo studies were performed with an aldehyde dehydrogenase 2 (ALDH2) alternated animal model. The pear extract (10 mL/kg bw) was administered to Aldh2 normal (C57BL/6) and deficient (Aldh2 -/-) male mice. After 30 min, ethanol (1 g or 2 g/kg bw) was administered to the mice via gavage. Levels of alcohol and acetaldehyde in blood were quantified by GC/MS. First, it was observed that the pears stimulated both alcohol dehydrogenase (ADH) and ALDH activities by 2â¼3- and 1.3-fold in in vitro studies, respectively. Second, mouse PK data (AUC(∞) and C(max) ) showed that the pear extract decreased the alcohol level in blood regardless of ALDH2 genotype. Third, the pear increased the acetaldehyde level in blood in Aldh2 deficient mice but not in Aldh2 normal mice. Therefore, the consistent in vitro and in vivo data suggest that Korean pears stimulate the two key alcohol-metabolizing enzymes. These stimulations could be the main mechanism of the Korean pear for alcohol detoxification. Finally, the results suggest that polymorphisms of human ALDH2 could bring out individual variations in the effects of Korean pear on alcohol detoxification.
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Aldehído Deshidrogenasa/metabolismo , Etanol/sangre , Inactivación Metabólica , Extractos Vegetales/farmacología , Pyrus/química , Acetaldehído/sangre , Alcohol Deshidrogenasa/metabolismo , Aldehído Deshidrogenasa Mitocondrial , Animales , Etanol/toxicidad , Genotipo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones NoqueadosRESUMEN
TNF-related apoptosis-inducing ligand (TRAIL) is a promising agent for management of cancer because of its selective cytotoxicity to cancer cells. However, some cancer cells have resistance to TRAIL. Accordingly, novel treatment strategies are required to overcome TRAIL resistance. Here, we examined the synergistic apoptotic effect of apigenin in combination with TRAIL in Huh-7 cells. We found that combined treatment of TRAIL and apigenin markedly inhibited Huh-7 cell growth compared to either agent alone by inducing apoptosis. Combined treatment with apigenin and TRAIL induced chromatin condensation and the cleavage of poly (ADP-ribose) polymerase (PARP). In addition, enhanced apoptosis by TRAIL/apigenin combination was quantified by annexin V/PI flow cytometry analysis. Western blot analysis suggested that apigenin sensitizes cells to TRAIL-induced apoptosis by activating both intrinsic and extrinsic apoptotic pathway-related caspases. The augmented apoptotic effect by TRAIL/apigenin combination was accompanied by triggering mitochondria-dependent signaling pathway, as indicated by Bax/Bcl-2 ratio up-regulation. Our results demonstrate that combination of TRAIL and apigenin facilitates apoptosis in Huh-7 cells.
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Wogonin is a one of the bioactive compounds of Scutellaria baicalensi Georgi which has been shown to have antiinflammatory, anticancer, antiviral and neuroprotective effects. However, the underlying mechanisms by which wogonin induces apoptosis in cancer cells still remain speculative. Here we investigated the potential activation of MAPKs and generation of reactive oxygen species (ROS) by wogonin on MCF-7 human breast cancer cells. These results showed that wogonin induced mitochondria and death-receptor-mediated apoptotic cell death, which was characterized by activation of several caspases, induction of PARP cleavage, change of antiapoptotic/proapoptotic Bcl-2 family member ratios and cleavage of Bid. We also found that generation of ROS was an important mediator in wogonin-induced apoptosis. Further investigation revealed that wogonin activated ERK and p38 MAPKs, which was inhibited by N-acetyl cysteine (NAC), a ROS scavenger, indicating that wogonin-induced ROS are associated with MAPKs activation. These data demonstrate that wogonin may be a novel anticancer agent for treatment of breast cancer.
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Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Flavanonas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Neoplasias de la Mama , Caspasa 8/metabolismo , Caspasa 9/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Activación Enzimática , Femenino , Humanos , Poli(ADP-Ribosa) Polimerasa-1 , Poli(ADP-Ribosa) Polimerasas/metabolismoRESUMEN
BACKGROUND: Pigmentation in human skin is an important defense mechanism against sunlight or oxidative stress. Despite the protective role of melanin, abnormal hyperpigmentation such as freckles and chloasma sometimes can be serious aesthetic problems. Because of these effects of hyperpigmentation, people have considered the effect of depigmentation. Azelaic acid (AZ) is a saturated dicarboxylic acid found naturally in wheat, rye, and barley. Previously, we showed that AZ inhibited melanogenesis. In this study, we investigated the antimelanogenic activity of combination of AZ and taurine (Tau) in B16F10 mouse melanoma cells. METHODS: The mouse melanoma cell line B16F10 was used in the study. We measured melanin contents and tyrosinase activity. To gain the change of protein expression, we carried out western blotting. RESULTS: We investigated that AZ combined with taurine (Tau) show more inhibitory effects in melanocytes than the treatment of AZ alone. AZ combined with Tau inhibited the melanin production and tyrosinase activity of B16F10 melanoma cells without significant cytotoxicity. Also inhibitory effects after treatment with these combined chemical are stronger than AZ alone on melanogenesis. CONCLUSIONS: These findings indicate that AZ with Tau might play an important role in the regulation of melanin formation and be useful as effective ingredients in antimelanogesis.
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Ácidos Dicarboxílicos/farmacología , Combinación de Medicamentos , Melaninas/biosíntesis , Melanocitos/efectos de los fármacos , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Taurina/farmacología , Animales , Línea Celular Tumoral , Ácidos Dicarboxílicos/metabolismo , Ácidos Dicarboxílicos/uso terapéutico , Humanos , Melanocitos/citología , Melanocitos/metabolismo , Melanoma/patología , Ratones , Factor de Transcripción Asociado a Microftalmía/metabolismo , Monofenol Monooxigenasa/metabolismo , Pigmentación , Neoplasias Cutáneas/patología , Taurina/metabolismo , Taurina/uso terapéuticoRESUMEN
Platycodin D (PD), a major constituent isolated from the root of Platycodon grandiflorum, has been suggested to possess anticancer activities, as indicated by its capabilities to induce mitotic arrest and apoptosis in several cancer cells. However, little is known of the underlying action mechanism. This study is the first to investigate the anticancer effect of PD in the human breast cancer cell, MCF-7. Our data showed that PD exhibited marked cell growth inhibition by inducing apoptosis. This induction was associated with activation of caspase-8 and -9 activities and poly(ADP-ribose) polymerase. PD triggered the mitochondrial apoptotic pathway, as indicated by up-regulation of levels of cellular Bax and down-regulation of levels of Bcl-2 and caspase-9 activation. We found that PD induced proteolytic activation of Bid, a member of the proapoptotic Bcl-2 family, implicating PD-induced apoptosis as possibly being functionally linked to a death receptor-mediated pathway. The PD treatment also was accompanied by an increase in cellular generation of reactive oxygen species, indicating that PD-induced apoptosis is likely to be mediated through mitochondrial dysfunction. In addition, we revealed that the mitogen-activated protein kinases, including extracellular signal-regulated kinase 1/2, c-Jun NH(2)-terminal kinase 1/2, and p38, which play important roles in apoptosis, were activated by treatment with PD. These results provide a basic mechanism for the anticancer properties of PD and suggest that PD is a promising candidate for chemotherapy and chemoprevention of breast cancer.
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Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/farmacología , Platycodon/química , Saponinas/farmacología , Triterpenos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de la Mama/metabolismo , Caspasa 8/metabolismo , Caspasa 9/metabolismo , Línea Celular Tumoral , Femenino , Humanos , Mitocondrias/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Raíces de Plantas , Poli Adenosina Difosfato Ribosa/metabolismo , Poli(ADP-Ribosa) Polimerasas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Receptores de Muerte Celular/metabolismo , Saponinas/aislamiento & purificación , Saponinas/uso terapéutico , Triterpenos/aislamiento & purificación , Triterpenos/uso terapéuticoRESUMEN
There is now increasing evidence that free radicals and reactive oxygen species (ROS) are involved in a variety of pathological events. Reactive oxygen species are produced during normal cellular function and lead to lipid peroxidation, massive protein oxidation and degradation. Taurine is an abundant free amino acid in inflammatory cells, where it is thought to be cytoprotective. The aim of the present study was to examine whether taurine enhances endogenous antioxidant enzyme activity and/or regulates ROS generation in B16F10 mouse melanoma cells. B16F10 cells were exposed to medium containing taurine for a period of 24 h. Cell viability, measured by the MTT assay, exhibited a dose-dose dependent inhibition. Taurine increased the activities of superoxide dismutase, glutathione peroxidase and CAT compared to those of the control, an effect paralleling an increase in gene expression. Taurine also reduced ROS content in a dose-dependent manner. Taken together, our results suggest that taurine decreases ROS levels by increasing the levels of the antioxidant enzymes.