RESUMEN

This study assessed the effects of fatty acid length and saturation on the physicochemical, thermal, and gastrointestinal digestive characteristics of curcumin-loaded homo-triacylglycerol nanoparticles (C-NPs). All C-NPs had good colloidal stability and efficiently entrapped curcumin, regardless of their length and saturation. Tricaprylin NPs, with shorter chains, had a smaller size and emulsifier surface load. Curcumin was released faster from low-melting C-NPs (tricaprylin and triolein) than those with high-melting-point (trimyristin, tripalmitin, and tristearin); however, both were negligible without lipolysis. None of the C-NPs underwent significant aggregation, coalescence, or breakdown during digestion before the small intestine. Notably, longer and more saturated chains resulted in a slower initial rate and lower degree of lipolysis in the small intestine. However, greater bioaccessibility of curcumin was observed only with longer chains (tricaprylin, 70.72%; trimyristin, 78.05%; tripalmitin, 85.09%; tristearin, 89.65%; triolein, 89.71%). These findings could be valuable for the development of rational curcumin formulations for functional foods.

Asunto(s)

Curcumina , Digestión , Nanopartículas , Triglicéridos , Curcumina/química , Curcumina/metabolismo , Nanopartículas/química , Triglicéridos/química , Triglicéridos/metabolismo , Humanos , Tracto Gastrointestinal/metabolismo , Portadores de Fármacos/química , Tamaño de la Partícula , Lipólisis

RESUMEN

AIMS: Doxorubicin (DOX) is a widely used anthracycline anticancer agent; however, its irreversible effects on the heart can result in DOX-induced cardiotoxicity (DICT) after cancer treatment. Unfortunately, the pathophysiology of DICT has not yet been fully elucidated, and there are no effective strategies for its prevention or treatment. In this investigation, the novel role of transducin beta-like protein 1 (TBL1) in developing and regulating DICT was explored. METHODS AND RESULTS: We observed a reduction in TBL1 protein expression levels as well as cleavage events in the transplanted cardiac tissues of patients diagnosed with Dilated Cardiomyopathy and DICT. It was revealed that DOX selectively induces TBL1 cleavage at caspase-3 preferred sites-D125, D136, and D215. Interestingly, overexpression of the uncleaved TBL1 mutant (TBL1uclv) variant reduced apoptosis, effectively preventing DOX-induced cell death. We confirmed that cleaved TBL1 cannot form a complex with ß-catenin. As a result, Wnt reporter activity and Wnt target gene expression collectively indicate a decrease in Wnt/ß-catenin signalling, leading to DICT progression. Furthermore, the cleaved TBL1 triggered DOX-induced abnormal electrophysiological features and disrupted calcium homeostasis. However, these effects were improved in TBL1uclv-overexpressing human-induced pluripotent stem cell-derived cardiomyocytes. Finally, in a DICT mouse model, TBL1uclv overexpression inhibited the DICT-induced reduction of cardiac contractility and collagen accumulation, ultimately protecting cardiomyocytes from cell death. CONCLUSION: Our findings reveal that the inhibition of TBL1 cleavage not only mitigates apoptosis but also enhances cardiomyocyte function, even in the context of DOX administration. Consequently, this study's results suggest that inhibiting TBL1 cleavage may be a novel strategy to ameliorate DICT.

Asunto(s)

Apoptosis , Cardiotoxicidad , Doxorrubicina , Miocitos Cardíacos , Vía de Señalización Wnt , beta Catenina , Doxorrubicina/farmacología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Miocitos Cardíacos/enzimología , Vía de Señalización Wnt/efectos de los fármacos , Humanos , Animales , Apoptosis/efectos de los fármacos , beta Catenina/metabolismo , beta Catenina/genética , Cardiomiopatía Dilatada/metabolismo , Cardiomiopatía Dilatada/patología , Cardiomiopatía Dilatada/inducido químicamente , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/enzimología , Cardiomiopatía Dilatada/fisiopatología , Masculino , Transducina/metabolismo , Transducina/genética , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Madre Pluripotentes Inducidas/enzimología , Células Madre Pluripotentes Inducidas/patología , Femenino , Estudios de Casos y Controles , Antibióticos Antineoplásicos/farmacología , Antibióticos Antineoplásicos/toxicidad

RESUMEN

Aqueous zinc-bromine batteries hold immense promise for large-scale energy storage systems due to their inherent safety and high energy density. However, achieving a reliable zinc metal electrode reaction is challenging because zinc metal in the aqueous electrolyte inevitably leads to dendrite growth and related side reactions, resulting in rapid capacity fading. Here, it is reported that combined cationic and anionic additives in the electrolytes using CeCl3 can simultaneously address the multiple chronic issues of the zinc metal electrode. Trivalent Ce3+ forms an electrostatic shielding layer to prevent Zn2+ from concentrating at zinc metal protrusions, while the high electron-donating nature of Cl- mitigates H2O decomposition on the zinc metal surface by reducing the interaction between Zn2+ and H2O. These combined cationic and anionic effects significantly enhance the reversibility of the zinc metal reaction, allowing the non-flow aqueous Zn─Br2 full-cell to reliably cycle with exceptionally high capacity (>400 mAh after 5000 cycles) even in a large-scale battery configuration of 15 × 15 cm2.

RESUMEN

In this paper, we propose a new type of vision transformer (ViT) based on graph head attention (GHA). Because the multi-head attention (MHA) of a pure ViT requires multiple parameters and tends to lose the locality of an image, we replaced MHA with GHA by applying a graph to the attention head of the transformer. Consequently, the proposed GHA maintains both the locality and globality of the input patches and guarantees the diversity of the attention. The proposed GHA-ViT commonly outperforms pure ViT-based models using small-sized CIFAR-10/100, MNIST, and MNIST-F datasets and a medium-sized ImageNet-1K dataset in scratch training. A Top-1 accuracy of 81.7% was achieved for ImageNet-1K using GHA-B, which is a base model with approximately 29 M parameters. In addition, with CIFAR-10/100, the existing ViT and parameters are reduced 17-fold and the performance increased by 0.4/4.3%, respectively. The proposed GHA-ViT shows promising results in terms of the number of parameters and operations and the level of accuracy in comparison with other state-of-the-art ViT-lightweight models.

RESUMEN

Introduction: We propose an automatic sleep stage scoring model, referred to as SeriesSleepNet, based on convolutional neural network (CNN) and bidirectional long short-term memory (bi-LSTM) with partial data augmentation. We used single-channel raw electroencephalography signals for automatic sleep stage scoring. Methods: Our framework was focused on time series information, so we applied partial data augmentation to learn the connected time information in small series. In specific, the CNN module learns the time information of one epoch (intra-epoch) whereas the bi-LSTM trains the sequential information between the adjacent epochs (inter-epoch). Note that the input of the bi-LSTM is the augmented CNN output. Moreover, the proposed loss function was used to fine-tune the model by providing additional weights. To validate the proposed framework, we conducted two experiments using the Sleep-EDF and SHHS datasets. Results and Discussion: The results achieved an overall accuracy of 0.87 and 0.84 and overall F1-score of 0.80 and 0.78 and kappa value of 0.81 and 0.78 for five-class classification, respectively. We showed that the SeriesSleepNet was superior to the baselines based on each component in the proposed framework. Our architecture also outperformed the state-of-the-art methods with overall F1-score, accuracy, and kappa value. Our framework could provide information on sleep disorders or quality of sleep to automatically classify sleep stages with high performance.

RESUMEN

Several oral bacteria, including Prevotella melaninogenica (Pm), have aquaporin (AQP) proteins homologous to human AQP5, a major water channel protein targeted in Sjogren's syndrome. This study aimed to understand the antigenic characteristics that induce autoantibodies against an AQP5 "E" epitope (AQP5E) in a mouse model using C57BL/6 mice. Immunization with a PmE-L peptide derived from Pm AQP, which contains amino acid mismatches both at the B- and T-cell epitopes, efficiently induced anti-AQP5E autoantibodies accompanied by increased germinal center (GC) B and follicular helper T cells in the draining lymph nodes. However, PmE, a peptide lacking a T-cell epitope, and AQP5E-L, an AQP5-derived self-peptide, hardly induced either anti-AQP5E autoantibodies or GC responses. Surprisingly, OTII-AQP5E, a peptide that replaced the self T-cell epitope of AQP5E-L with an ovalbumin-derived foreign T-cell epitope, was not any better than AQP5E-L in the induction of anti-AQP5E autoantibodies and GC response, despite the substantial expansion of CD4+ T cells and production of anti-OTII-AQP5E antibodies. The complex of biotinylated PmE-L peptide and highly immunogenic streptavidin (SA) induced a strong extrafollicular B-cell response skewed toward the expansion of SA-specific B cells. However, the expansion of AQP5E-specific GC B cells was limited, resulting in the inefficient induction of anti-AQP5E autoantibodies. Collectively, our results have demonstrated that anti-AQP5E autoantibody production is only allowed when foreign B- and T-cell epitopes drive a strong GC response of AQP5E-specific B cells for affinity maturation. This study helps explain why cross-reactive anti-AQP5 autoantibodies are not produced during the immune response to Pm in most healthy people.

RESUMEN

Herein, a novel combination of Mg- and Ga-co-doped ZnO (MGZO)/Li-doped graphene oxide (LGO) transparent electrode (TE)/electron-transporting layer (ETL) has been applied for the first time in Cu2 ZnSn(S,Se)4 (CZTSSe) thin-film solar cells (TFSCs). MGZO has a wide optical spectrum with high transmittance compared to that with conventional Al-doped ZnO (AZO), enabling additional photon harvesting, and has a low electrical resistance that increases electron collection rate. These excellent optoelectronic properties significantly improved the short-circuit current density and fill factor of the TFSCs. Additionally, the solution-processable alternative LGO ETL prevented plasma-induced damage to chemical bath deposited cadmium sulfide (CdS) buffer, thereby enabling the maintenance of high-quality junctions using a thin CdS buffer layer (≈30 nm). Interfacial engineering with LGO improved the Voc of the CZTSSe TFSCs from 466 to 502 mV. Furthermore, the tunable work function obtained through Li doping generated a more favorable band offset in CdS/LGO/MGZO interfaces, thereby, improving the electron collection. The MGZO/LGO TE/ETL combination achieved a power conversion efficiency of 10.67%, which is considerably higher than that of conventional AZO/intrinsic ZnO (8.33%).

RESUMEN

Uncontrollable Zn dendrite formations and parasitic side reactions on Zn electrodes induce poor cycling stability and safety issues, preventing the large-scale commercialization of Zn-ion batteries. Herein, to achieve uniform Zn deposition and suppress side reactions, an electrospun ferroelectric poly(vinylidene fluoride-co-trifluoroethylene) copolymer, a P(VDF-TrFE) nanofiber layer, is introduced as an artificial solid-electrolyte interface on a Cu substrate acting as a current collector. The aligned molecular structure of ß-P(VDF-TrFE) can effectively suppress localized current density on the Cu surface, lead to uniform Zn deposition, and suppress side reactions by preventing direct contact between electrodes and aqueous electrolytes. The half-cell configuration formed by the newly fabricated electrode can achieve an average coulombic efficiency of 99.2% over 300 cycles without short-circuiting at a current density of 1 mA cm-2 and areal capacity of 1 mAh cm-2. Stable cycling stability is also maintained for 200 cycles at a current density of 0.5 A g-1 in a full-cell test using MnO2 as a cathode.

RESUMEN

[This corrects the article DOI: 10.1371/journal.pone.0267908.].

RESUMEN

Lithium-ion batteries with ultra-thick electrodes have high energy density and low manufacturing costs because of the reduction of the inactive materials in the same battery volume. However, the partial usage of the full capacity and the low rate capability are caused by poor ionic and electronic conduction. In this work, the effects of two approaches, such as electrode binder carbonization by heat treatment and 3-dimensionalization by the laser structuring of ultra-thick graphite anodes to lithium-ion batteries for high energy density, are investigated. During the heat treatment, the polyvinylidene fluoride (PVDF) binder is carbonized to form fluorinated graphitic carbons, thereby increasing the number of lithium-ion storage sites and the improvement of the electrode capacity by 14% (420 mAh g-1 and 20 mAh cm-2). Further, the carbonization improves the rate capability by 31% at 0.1 C by simultaneously reducing the ionic and electronic resistances. Furthermore, after the laser structuring of the carbonized electrode, the areal discharge capacity increases to 50% at the increasing current rates, resulting from drastically improved ionic conduction. In addition to the electrochemical characteristics, these two approaches contribute considerably to the fast wetting of the electrolyte into the ultra-thick electrode. The carbonization and laser structuring of the ultra-thick graphite anodes are practical approaches for high-energy batteries to overcome the thickness limitation.

RESUMEN

Hypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disease and is characterized by hypertrophy of the left ventricle. We reprogrammed peripheral blood mononuclear cells (PBMCs) from a HCM patient into pluripotent stem cells (iPSC) (YCMi006-A) carrying a heterozygous c.1029C > G mutation in ACTA1. The YCMi006-A cells expressed high levels of pluripotent markers, had a normal 46XX karyotype and demonstrated the capacity to differentiate into derivatives of all three germ layers. This cell line can be a valuable tool for investigating the pathogenesis of HCM.

Asunto(s)

Cardiomiopatía Hipertrófica , Línea Celular , Células Madre Pluripotentes Inducidas , Cardiomiopatía Hipertrófica/patología , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Leucocitos Mononucleares/metabolismo , Mutación/genética

RESUMEN

With the development of cloud computing, interest in database outsourcing has recently increased. In cloud computing, it is necessary to protect the sensitive information of data owners and authorized users. For this, data mining techniques over encrypted data have been studied to protect the original database, user queries and data access patterns. The typical data mining technique is kNN classification which is widely used for data analysis and artificial intelligence. However, existing works do not provide a sufficient level of efficiency for a large amount of encrypted data. To solve this problem, in this paper, we propose a privacy-preserving parallel kNN classification algorithm. To reduce the computation cost for encryption, we propose an improved secure protocol by using an encrypted random value pool. To reduce the query processing time, we not only design a parallel algorithm, but also adopt a garbled circuit. In addition, the security analysis of the proposed algorithm is performed to prove its data protection, query protection, and access pattern protection. Through our performance evaluation, the proposed algorithm shows about 2∼25 times better performance compared with existing algorithms.

Asunto(s)

Nube Computacional , Privacidad , Algoritmos , Inteligencia Artificial , Seguridad Computacional

RESUMEN

A benzothiazole-based fluorescent and colorimetric chemosensor BZD ((E)-2-(benzo[d]thiazol-2-yl)-5-((4-(diethylamino)-2-hydroxybenzylidene)amino)phenol) was applied for detecting ClO-. BZD showed fluorescence quenching and color variation for ClO- via oxidative reaction between ClO- and the imine bond. It could effectively detect ClO- over various competitive analytes. Detection limit for ClO- was calculated to be 1.74 µM by fluorescent method and 16.44 µM by colorimetric one, respectively. Additionally, BZD could be utilized for sensing ClO- in zebrafish, real water sample and paper strip. The photophysical characteristics and sensing mechanism of BZD to ClO- were studied by fluorescent and UV-visible spectroscopy, NMR titration, and ESI-mass spectrometry.

Asunto(s)

Colorimetría , Ácido Hipocloroso , Animales , Benzotiazoles , Colorantes Fluorescentes , Agua , Pez Cebra

RESUMEN

Quantum dot (QD)-based luminescent down-shifting (LDS) layers were deposited on Cu2ZnSn(S,Se)4 (CZTSSe) solar cells via the drop-casting method. The LDS layers can easily widen the narrow absorption wavelength regions of single-junction solar cells and enable improvement of the short-circuit current. The optical properties of LDS layers deposited on glass and containing different QD contents were analyzed based on their transmittance, reflectance, and absorbance. The absorber films to be used in the CZTSSe solar cells were determined by X-ray diffraction measurements and Raman spectroscopy to determine their crystal structures and secondary phases, respectively. The completed CZTSSe solar cells with LDS layers showed increased ultraviolet responses of up to 25% because of wavelength conversion by the QDs. In addition, the impact of the capping layer, which was formed to protect the QDs from oxygen and moisture, on the solar cell performance was analyzed. Thus, a maximal conversion efficiency of 7.3% was achieved with the 1.0 mL QD condition; furthermore, to the best of our knowledge, this is the first time that LDS layers have been experimentally demonstrated for CZTSSe solar cells.

RESUMEN

Silymarin is a purified mixture of four isomeric flavonoids extracted from the seeds and fruit of the milk thistle plant, Silybum marianus (L.). Silymarin exhibits a wide variety of biological effects and is commonly used in traditional medicine. Therefore, the anticancer effects of silymarin on human breast cancer cells were investigated to determine its pharmacological mechanisms in vitro and in vivo. The viability and proliferation of MDA-MB- 231 and MCF-7 breast cancer cells were investigated using MTT and wound healing assays. Silymarin decreased the viability and proliferation of MDA-MB-231 and MCF-7 cells in a concentration-dependent manner. The number of apoptotic bodies, as shown by DAPI staining, was increased in a concentration-dependent manner, indicating that silymarin induces apoptosis. Additionally, changes in the expression levels of apoptosis-related proteins were demonstrated in human breast cancer cells using western blotting. Silymarin increased the levels of Bax, cleaved poly-ADP ribose polymerase, cleaved caspase-9 and phosphorylated (p-)JNK, and decreased the levels of Bcl-2, p-P38 and p-ERK1/2. Furthermore, the inhibitory effects of silymarin on MCF-7 tumor growth were investigated. In mice treated with silymarin for 3 weeks (25 and 50 mg/kg), MCF-7 tumor growth was inhibited without organ toxicity. In MCF-7 tumors, silymarin induced apoptosis and decreased p-ERK1/2 levels, as assessed using a TUNEL assay and immunohistochemistry. These results indicated that silymarin inhibited breast cancer cell proliferation both in vitro and in vivo by modulating the MAPK signaling pathway. Therefore, silymarin may potentially be used as a chemo-preventive or therapeutic agent.

RESUMEN

Aronia, a healthy fruit well known as black chokeberry, has health-promoting effects on hypertension, oxidative stress, and diabetes. Despite many reports of bioactivities of aronia, there is little scientific research on the potential for immune-enhancement. So, anthocyanin-fucoidan nanocomplex (AFNC, a nanocomplex of aronia extract and fucoidan) has been developed to improve immune-enhancement. This study aimed to identify immunomodulatory effects and underlying mechanisms of AFNC using RAW264.7 macrophages and cyclophosphamide-induced immunosuppressed mice. As a result, AFNC-treated RAW264.7 macrophages elevated the production of IL-2, IL-6, tumor necrosis factor (TNF)-α, and nitric oxide (NO). AFNC-enhanced inducible NO synthase expression via nuclear factor-κB signaling pathways. AFNC dose-dependently increased levels of IL-2, IL-6, TNF-α, IL-10, IL-12, interferon-γ, or IL-4 in the serum and spleen of immunosuppressed mice. Taken together, AFNC encourages the immune-enhancing activity through immunostimulatory cytokine production by activation of macrophage. Therefore, these results suggest that AFNC is useful for immunodeficiency-related disorders. PRACTICAL APPLICATIONS: In these days of prevalence of infectious diseases, individual immunity is very important. AFNC has the immune-enhancing effects through immunostimulatory cytokine production by activation of macrophage. Therefore, AFNC could be widely applied to ameliorate a variety of diseases caused by immunosuppression such as infectious diseases.

Asunto(s)

Antocianinas , Macrófagos , Animales , Ciclofosfamida , Ratones , Polisacáridos

RESUMEN

Apigenin, an aromatic compound, exhibits antioxidant, anti­inflammatory and anti­viral effects. The present study aimed to investigate the effects of apigenin on cell proliferation and apoptosis of human melanoma cells A375P and A375SM. Therefore, melanoma cells were treated with apigenin to determine its anti­proliferative and survival effects, using wound healing and MTT assays. The results revealed that melanoma cell viability was decreased in a dose­dependent manner. Furthermore, chromatin condensation, indicating apoptosis, was significantly increased in a dose­dependent manner, as demonstrated by DAPI staining. In addition, increased apoptosis rate following treatment with apigenin was confirmed by Annexin V­propidium iodide staining. The changes in the expression levels of apoptosis­related proteins in A375P and A375SM melanoma cells were subsequently detected using western blot analysis. The results demonstrated that the protein expression levels of Bcl­2 were decreased, whereas those of Bax, cleaved poly ADP­ribose polymerase, cleaved caspase­9 and p53 were upregulated in a dose­dependent manner in apigenin­treated cells compared with those noted in untreated cells. In addition, in apigenin­treated A375P cells, phosphorylated (p)­p38 was upregulated and p­extracellular signal­regulated kinase (ERK), p­c­Jun N­terminal kinase (JNK) and p­protein kinase B (Akt) were downregulated. However, in A375SM cells, apigenin treatment increased p­ERK and p­JNK and decreased p­p38 and p­Akt protein expression levels. Subsequently, the inhibitory effect of apigenin on tumor growth was investigated in vivo. Tumor volume was significantly reduced in the 25 and 50 mg/kg apigenin­treated groups compared with the control group. Additionally, a TUNEL assay was performed to detect apoptotic cells. Immunohistochemical staining also revealed elevated p­ERK expression in the apigenin­treated group compared with the control group. Overall, the findings of the present study indicated that apigenin attenuated the growth of A375SM melanoma cells by inducing apoptosis via regulating the Akt and mitogen­activated protein kinase signaling pathways.

Asunto(s)

Apigenina/farmacología , Melanoma/metabolismo , Animales , Apigenina/metabolismo , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/metabolismo , Caspasa 9/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , China , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Melanoma/tratamiento farmacológico , Ratones , Ratones Endogámicos BALB C , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo

RESUMEN

Event-related potential (ERP) speller can be utilized in device control and communication for locked-in or severely injured patients. However, problems such as inter-subject performance instability and ERP-illiteracy are still unresolved. Therefore, it is necessary to predict classification performance before performing an ERP speller in order to use it efficiently. In this study, we investigated the correlations with ERP speller performance using a resting-state before an ERP speller. In specific, we used spectral power and functional connectivity according to four brain regions and five frequency bands. As a result, the delta power in the frontal region and functional connectivity in the delta, alpha, gamma bands are significantly correlated with the ERP speller performance. Also, we predicted the ERP speller performance using EEG features in the resting-state. These findings may contribute to investigating the ERP-illiteracy and considering the appropriate alternatives for each user.

Asunto(s)

Interfaces Cerebro-Computador , Encéfalo , Electroencefalografía , Potenciales Evocados , Lóbulo Frontal , Humanos

RESUMEN

Sleep disorder is one of many neurological diseases that can affect greatly the quality of daily life. It is very burdensome to manually classify the sleep stages to detect sleep disorders. Therefore, the automatic sleep stage classification techniques are needed. However, the previous automatic sleep scoring methods using raw signals are still low classification performance. In this study, we proposed an end-to-end automatic sleep staging framework based on optimal spectral-temporal sleep features using a sleep-edf dataset. The input data were modified using a bandpass filter and then applied to a convolutional neural network model. For five sleep stage classification, the classification performance 85.6% and 91.1% using the raw input data and the proposed input, respectively. This result also shows the highest performance compared to conventional studies using the same dataset. The proposed framework has shown high performance by using optimal features associated with each sleep stage, which may help to find new features in the automatic sleep stage method.Clinical Relevance- The proposed framework would help to diagnose sleep disorders such as insomnia by improving sleep stage classification performance.

Asunto(s)

Electroencefalografía , Trastornos del Sueño-Vigilia , Humanos , Redes Neurales de la Computación , Sueño , Fases del Sueño

RESUMEN

In this study, we investigated whether Quercetin has anti-cancer effects on A375SM and A375P human melanoma cells. Cell viability was assessed using an MTT assay. The proliferation of melanoma cells was measured by a wound-healing assay. Quercetin significantly decreased viability and proliferation of A375SM cells in a concentration-dependent manner. However, quercetin had no effect on A375P cells. DAPI staining showed increased chromatin condensation in a concentration-dependent manner, indicating apoptosis. Flow cytometric analysis indicated that quercetin suppressed the viability of A375SM cells by inducing apoptosis. Expression of quercetin-induced apoptosis proteins was investigated by Western blot analysis. Quercetin increased the expression of Bax, phospho-JNK, phospho-p38 and phospho-ERK1/2, cleaved poly-ADP ribose polymerase and decreased Bcl-2 in a concentration-dependent manner. We also investigated the in vivo tumor-growth inhibitory effect of quercetin. Quercetin (at 50 and 100 mg/kg) significantly decreased the A375SM tumor volume compared to the control group and increased apoptosis as assessed by the TUNEL assay. Immunohistochemistry staining revealed that the level of phosphor-JNK and phosphor-p38 increased in the quercetin-treated mice. These results indicate that quercetin inhibited the growth of A375SM melanoma cells through apoptosis and thus can be regarded as a new and effective chemo-preventive or therapeutic agent.

Asunto(s)

Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Melanoma/patología , Quercetina/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Femenino , Humanos , Ratones , Ensayos Antitumor por Modelo de Xenoinjerto