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1.
J Cancer ; 14(6): 989-1000, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37151389

RESUMO

Purpose: The long-term prognosis and survival rate of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are poor, although the identification of specific biomarkers that reveal its nature and aggressiveness has improved it. Growth-related oncogene alpha (Groα) and NOD1 (nucleotide-binding oligomerization domain 1) can be used as prognosis markers to identify subgroups of HNSCC patients with low survival rates and as potential therapeutic targets for HNSCC patients. However, the mechanism associated with the Groα-mediated NOD pathway in HNSCC progression remains unclear. Method: Overall survival analysis and multiple-gene comparison were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA). qRT-PCR and RT-PCR were used to analyze mRNA expression. Microarray, immunofluorescence staining or western blot analyses were carried out to detect protein expression. Results: Groα was significantly higher in the grade 4 HNSCC tumor tissues compared with that in grade 1-3 and healthy subjects. High expression of Groα, NOD1 and RIPK2 (receptor-interacting serine-threonine kinase 2) is correlated with survival rate in HNSCC patients. Treatment of SCC25 and OECM-1 cells with Groα increased the expression of NOD1 and RIPK2 in a concentration-dependent manner. The findings herein reveal the association of Groα, NOD1 and RIPK2 biomarkers with HNSCC carcinogenesis. Moreover, Groα is the major stimulus of inflammatory mediation and promotes TNF-α (tumor necrosis factor-α) and COX-2 (cyclooxygenase-2) expression in HNSCC. Groα induces TNF-α and COX-2 expression through regulation involving ERK (extracellular signal-regulated kinase)-, JNK (C-Jun N-terminal kinase)- and p38 MAPK (mitogen-activated protein kinase)-dependent signaling pathways. Conclusions: Our findings herein constitute the first evidence that Groα is important in HNSCC progression and metastasis via the NOD1-mediated MAPK pathway, suggesting a role for Groα and NOD1 in mediating metastasis and its potential as a therapeutic target.

2.
Life Sci ; 306: 120791, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35817169

RESUMO

Squamous cell carcinoma (SCC) is the most common malignant tumor of the head and neck and generally detected in the late stages when the cancer has advanced, and therefore has a poor prognosis and survival rate. A high expression of growth-related oncogene alpha (Groα) is associated with tumor metastasis and invasion and the poor survival rate of patients. Microarray reveals that Groα exhibits a cancer-specific response in HNSCC. Quantitative real-time PCR (qRT-PCR) results concerning the mRNA expression of Groα in HNSCC tissues; indicate that Groα was more highly expressed in HNSCC than in non-cancerous matched tissue (NCMT). The serum of HNSCC patients and healthy subjects demonstrates that the expression of Groα in the HNSCC patients significantly exceeded than in healthy subjects. Furthermore, exposure Groα to stimulated the proliferation, clonogenicity and migration with HNSCC cells (SCC4, SCC9, SCC25 and OECM-1), yielding a stronger response than in non-malignant HaCaT and DOK cells. A high expression of Groα and its receptors CXCR1/2 (chemokine (C-X-C motif) receptor) in HNSCC tissues are highly correlated with tumor progression stage and metastasis. Following the treatment of SCC25 and OECM-1 cells with Groα, ß-catenin, matrix metalloproteinases (MMP)-2, MMP-7 and MMP-9 expressions significantly increased but E-cadherin expression was slightly decreased, suggesting that the EMT and metastasis processes were activated by Groα. These findings constitute the first evidence that Groα promotes epithelial mesenchymal transition (EMT) and MMPs expressions in HNSCC via activating CXCR1/2, suggesting a role for Groα in mediating metastasis and its potential as a therapeutic target.


Assuntos
Transição Epitelial-Mesenquimal , Neoplasias de Cabeça e Pescoço , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Humanos , Metaloproteinases da Matriz/genética , Invasividade Neoplásica/genética , Oncogenes , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
3.
J Cosmet Dermatol ; 21(7): 2945-2953, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34636463

RESUMO

BACKGROUND: Djulis (Chenopodium formosanum Koidz.) is a cereal food and its antioxidant and pigment constituents may protect skin from photoaging, but conclusive experiments have not been carried out. OBJECTIVE: This investigation evaluates the effects of djulis extract as a functional supplement. PATIENTS/METHODS: In this study, the effects of djulis functional drinks on the free radical scavenging activities, promotion of collagen synthesis and protection against oxidative stress and the effects of ultraviolet B (UVB)-irradiated of pUC119 DNA were explored. Thirty healthy subjects (aged 35-55 years old) were randomly allocated to djulis or placebo drinks groups (50 ml of a djulis/placebo drink daily for 8 weeks for each subject) in a double-blind crossover study. RESULTS: The regular consumption of the djulis functional drinks significantly increased levels of the serum biochemical superoxide dismutase (SOD) and catalase (+9.5% and +124.8%) after 8 weeks, relative to baseline controls. The improvements in skin moisture, brightness, elasticity, crow's feet, texture, wrinkles, pores, and collagen content after 8 weeks in the djulis group were +13.3%, +3.8%, +13.2%, -21.8%, -12.1%, -11.0%, -1.4%, and +33.7%, respectively, relative to the baseline without treatment. CONCLUSIONS: These work findings suggest the daily consumption of djulis drinks can protect the skin against oxidative stress-induced damage, delay skin aging and improve skin conditions.


Assuntos
Antioxidantes , Envelhecimento da Pele , Adulto , Antioxidantes/farmacologia , Colágeno , Estudos Cross-Over , Suplementos Nutricionais , Voluntários Saudáveis , Humanos , Pessoa de Meia-Idade , Estresse Oxidativo , Pele , Raios Ultravioleta/efeitos adversos
4.
J Cosmet Dermatol ; 21(5): 2189-2199, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34265165

RESUMO

BACKGROUND: Coffee and coffee products are known potentially to reduce levels of oxidative stress biomarkers in humans. OBJECTIVE: This investigation evaluates the effects of coffee pulp extract as a functional supplement (in coffee pulp drink, CPD) and a cosmetic ingredient (coffee pulp serum, CPS). PATIENTS/METHODS: The effects of CPD and CPS for anti-oxidation and anti-aging were investigated. Forty subjects were randomly allocated to CPD or placebo drink groups (50 ml of a CPD/placebo drink daily for 8 weeks for each subject), and another 40 subjects were recruited to CPS or placebo serum groups (about 3 ml of a CPS/placebo serum day and night/daily for 4 weeks for each subject) in a double-blind study. RESULTS: The CPD and CPS (20%) can increase free radical scavenging activities by 93.3% and 85% (p < 0.001) for DPPH, 94.5% and 61.3% (p < 0.01) for ABTS·+ , 43.8% and 15.3% (p < 0.05) for NO· than placebo. The inhibition of tyrosinase activity was increased by 91.6% and 51.0% (p < 0.05) after CPD and CPS application. The CPD comprehensively improved the moisture, brightness, elasticity, spotting, texture, and collagen content of skin for most subjects after 8 weeks, relative to the baseline without treatment (p < 0.05). After 4 weeks of CPS serum consumption, the brightness, elasticity, spotting, UV spots, and collagen content of skin were slightly better than those at week 0 (p < 0.05). CONCLUSIONS: The daily consumption of coffee pulp extract products can slow the skin aging process and improve skin health.


Assuntos
Antioxidantes , Envelhecimento da Pele , Envelhecimento , Antioxidantes/farmacologia , Café , Colágeno , Método Duplo-Cego , Voluntários Saudáveis , Humanos , Extratos Vegetais/farmacologia
5.
J Cosmet Dermatol ; 21(5): 2236-2245, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34416060

RESUMO

BACKGROUND: Punica granatum (pomegranate) potentially ameliorates skin inflammation and pain, including herpetic stromal keratitis. Fermentation is a biotechnological technique that may naturally induce health benefits by producing antioxidants. However, the anti-aging effect of fermented pomegranate extracts (FPE) on the skin is still unclear. AIM: This investigation evaluates the effects of fermented pomegranate as a functional supplement (FPE drink, FPE-D) and a cosmetic ingredient (FPE serum, FPE-S) in vitro and in vivo. PATIENTS/METHODS: The effects of FPE products for anti-oxidation, anti-tyrosinase, anti-inflammation, and anti-aging were examined. Forty subjects were randomly allocated to FPE-D or placebo drink groups (50 ml of a FPE-D /placebo drink daily for 8 weeks for each subject), and another 40 subjects were recruited to FPE-S or placebo serum groups (about 3 ml of a FPE-S /placebo serum daily and nightly/daily for 4 weeks for each subject) in a double-blind study. RESULTS: The effects of FPE products on the DPPH, ABTS+ , and NO· free radical scavenging activities, their inhibiting of tyrosinase activity and their enhancement of the skin health of healthy subjects, were investigated. FPE-D improved the moisture, brightness, elasticity, and collagen density of the skin of most subjects at 8 weeks relative to the baseline without treatment (p < 0.05). After 4 weeks of FPE-S serum consumption, the moisture, brightness, elasticity, spots, UV spots, and collagen density of skin were slightly better than those at week 0 (p < 0.05). CONCLUSIONS: The daily consumption of fermented pomegranate extracts can protect the skin against oxidative stress and slow skin aging.


Assuntos
Punica granatum , Envelhecimento da Pele , Envelhecimento , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Humanos , Estresse Oxidativo , Extratos Vegetais
6.
J Cosmet Dermatol ; 20(1): 188-194, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32530124

RESUMO

BACKGROUND: The efficacy of Djulis for skin care is currently based on cellular or animal models, and the clinical aspect is not in place. AIM: This clinical study is to investigate the synergistic effect of fish collagen and Djulis (Chenopodium formosanum Koidz.) for improvement of skin parameters. We used the combination of hydrolyzed collagen and Djulis to develop a new functional formula for skin improvement. PATIENTS/METHODS: Fifty volunteers were randomly allocated (in a 1:1 ratio) to the placebo or collagen drink group. Volunteers were required to consume a 50 mL of a collagen drink or placebo drink daily for 8 weeks. For measurements, the indexes of skin conditions were measured at the baseline and 4 and 8 weeks. RESULTS: The improvements of skin hydration, brightness, crow's feet, texture, wrinkles, pores, spots, and collagen content after 8 weeks in collagen group were 17.8%, 5.4%, 14.9%, 9.9%, 29.3%, 10.4%, 9.9%, and 22.3%, respectively. Noticeably, over 68% of subjects got improved for their skin parameters after 8-week intake of collagen drink. The improvement levels indicated competitive skin improvement effects in comparison with previous studies. CONCLUSION: This clinical study demonstrates the synergistic effect of fish collagen and Djulis (the main components) for the substantial improvements in hydration, brightness, crow's feet, texture, wrinkles, pores, surface spots, and collagen content in skin. The collagen drink comprehensively improved skin parameters for most subjects after 4-week intake and manifested competitive efficiency in comparison with other similar studies. We convince that the collagen drink may delay skin aging process and improve skin aging parameters.


Assuntos
Envelhecimento da Pele , Animais , Colágeno , Método Duplo-Cego , Humanos , Pele
7.
Phytomedicine ; 63: 153005, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31302316

RESUMO

BACKGROUND: 8-Hydroxyquinoline derivatives have highly sensitive fluorescent chemosensors for metal ions, which are associated with anti-oxidant, anti-tumor and anti-HIV-1 properties. Head and neck squamous cell carcinoma (HNSCC) is associated with a high rate of mortality and novel anti-HNSCC drugs must be developed. Therefore, effective chemotherapy agents are required to address this public health issue. HYPOTHESIS/PURPOSE: The aim of this study was to investigate the inhibitory effect of tris(8-hydroxyquinoline)iron (Feq3) on the HNSCC and the underlying mechanism. STUDY DESIGN/METHODS: A novel 8-hydroxyquinoline derivative, Feq3, was synthesized. The cell viabilities were analyzed using MTT reagent. Apoptosis and the cell cycle distributions were determined by flow cytometer. Reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence, western blot, MitoSOX and CellROX stain assay were used to study the mechanism of Feq3. Feq3 combined with antioxidants NAC (N-acetylcysteine) and BSO (buthionine sulfoximine) measured the cell viability and intracellular ROS. RESULTS: Feq3 induced the death of HNSCC cells and caused them to exhibit the morphological features of apoptosis. Feq3 also induced apoptosis of SCC9 cells by cell cycle arrest during the G2/M phase and the induced arrest of SCC25 cells in the G0/G1 and G2/M phases, which was associated with decreased cyclin B1/cdc2 and cyclin D/cdk4 expressions. Feq3 increases reactive oxygen species (ROS) and reduces glutathione (GSH) levels, and responds to increased p53 and p21 expressions. Feq3 induced apoptosis by mitochondria-mediated Bax and cytochrome c up-expression and down-expression Bcl-2. Feq3 also up-regulated tBid, which interacts with the mitochondrial pathway and tumor necrosis factor-α (TNF-α)/TNF-Rs, FasL/Fas, and TNF-related apoptosis inducing ligand receptors (TRAIL-Rs)/TRAIL-dependent caspases apoptotic signaling pathway in HNSCC cells. However, Feq3 activates Fas but not FasL in SCC25 cells. Feq3 arrests the growth of HNSCC cells and is involved in the mitochondria- and death receptor (DR)-mediated caspases apoptotic pathway. CONCLUSION: This study is the first to suggest that apoptosis mediates the anti-HNSCC of Feq3. Feq3 has potential as a cancer therapeutic agent against HNSCC.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Hidroxiquinolinas/farmacologia , Compostos de Ferro/farmacologia , Ferro/química , Estresse Oxidativo/efeitos dos fármacos , Quinolinas/farmacologia , Apoptose/fisiologia , Caspases/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/metabolismo , Proteína Ligante Fas/metabolismo , Glutationa/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Compostos de Ferro/uso terapêutico , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Quinolinas/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Receptores de Morte Celular/metabolismo , Transdução de Sinais/efeitos dos fármacos
8.
J Food Sci Technol ; 55(6): 2310-2317, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29892131

RESUMO

Milkfish (Chanos chanos), which is resistant to water quality changes is the fourth largest aquaculture commodity. Abandoned wastes of fish scale and bones aggravate environmental pollution. In this study, the effect of collagen peptides isolated from milkfish scales (MSCP) by pepsin-soluble collagen method on cell viability was investigated. The antioxidant, anti-inflammatory, and DNA-protective activities of MSCP were also evaluated. Results revealed that more than 95% of viable cells were retained in human keratinocytes after addition of 100 mg/mL MSCP. Measurement of DPPH· and ABTS· + radical scavenging activities and cellular reactive oxygen species revealed the high antioxidant activities of MSCP. MSCP demonstrated anti-inflammatory activities by reducing lipoxygenase activity and nitric oxide (NO·) radicals. Moreover, DNA electrophoresis assay indicated that MSCP treatment can directly protect against cyclobutane di-pyrimidine production and DNA single-strand breaks, which are harmful effects of UV radiation and H2O2. Given its antioxidant, anti-inflammatory, and DNA-protective activities, MSCP has potential applications in cosmeceuticals and supplementary health food.

9.
Oncotarget ; 8(34): 56375-56388, 2017 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-28915597

RESUMO

This investigation identifies interleukin 8 (IL-8) as the main inflammatory mediator in head and neck squamous cell carcinoma (HNSCC). The expressions of chemokines of IL-8, IL-1ß and IL-6 and the cytokines of tumor necrosis factor-α (TNF-α) were higher in HNSCC patient tissues than in non-cancerous matched tissues (NCMT) whereas the expression of IL-10 was lower. IL-8 is most highly expressed in the tissues of patients with HNSCC. Treatment of HNSCC cells with IL-8 increased the secretion of IL-1ß, IL-6 and TNF-α and reduced IL-10 expression; the increase in the expression of IL-1ß was particularly considerable. IL-8 silencing by siRNA reduced IL-1ß expression in HNSCC cells, suggesting that IL-8 as a main inflammatory mediator improved IL-1ß expression in HNSCC. The expressions of p-p38 mitogen-activated protein kinases (MAPK) and p-extracellular signal regulated kinase (p-ERK) were higher and that of p-c-Jun-NH2-terminal kinase (p-JNK) was lower in HNSCC patient tissues than in NCMT. IL-8 treatment induced p-p38 MAPK and p-ERK expression, but reduced p-JNK expressions in HNSCC cells. IL-8 siRNA suppressed p38 MAPK and ERK but increased JNK expression in HNSCC cells. Exposure of SCC25 cells to IL-8, increased the expressions of p-IκB-α and nuclear factor (NF)-κB, suggesting that IL-8 regulates inflammatory response by modulating the MAPK and NF-κB pathway in HNSCC cells. IL-8 promotes the migration of SCC25 cells and increases matrix metalloproteinase-2 (MMP-2) and MMP-9 expressions. These results reveal that IL-8 is the major stimulus of inflammatory mediation in HNSCC progression and migration by activating the p38 MAPK/ERK-NF-κB pathway and reducing JNK.

10.
Oncotarget ; 7(38): 61820-61831, 2016 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-27557518

RESUMO

NOD1 (nucleotide-binding oligomerization domain 1) is overexpressed in head and neck squamous cell carcinoma (HNSCC) cells, as is IL-8 in cancer cells. However, the mechanism of the IL-8-mediated overexpression of NOD in HNSCC not been identified. This study determines whether IL-8 promotes tumor progression via the NOD signaling pathway in HNSCC. Higher IL-8, NOD1 and receptor-interacting protein kinase (RIP2) expressions were observed in HNSCC tissue than in non-cancerous matched tissue (NCMT), whereas NOD2 was weakly expressed. Furthermore, IL-8 stimulated the proliferation of HNSCC cells (SCC4, SCC9 and SCC25) but not dysplastic oral mucosa DOK cells. Exposure to IL-8 increased the clonogenicity of HNSCC cells. IL-8 siRNA inhibited cell proliferation and cell colony formation, suggesting that IL-8 is involved in HNSCC cancer progression. The expressions of CXCR1 and CXCR2 were higher in HNSCC tissue than in NCMT. HNSCC cells that were exposed to IL-8 exhibited higher expression of CXCR1/2 than did controls. The blocking of IL-8 by siRNA reduced CXCR1/2 expression in HNSCC cells, suggesting that the cancer progression of HNSCC cells that is induced by IL-8 depends on CXCR1/2. Additionally, IL-8 is associated with increased NOD1 and RIP2 expression and reduced NOD2 expression in three types of HNSCC cells. The blocking of IL-8 by siRNA reduces IL-8, NOD1 and RIP2 expressions in HNSCC cells, but not the level of NOD2. These results suggest that IL-8 has an important role in HNSCC progression via a CXCR1/2-meidated NOD1/RIP2 signaling pathway.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Interleucina-8/metabolismo , Proteína Adaptadora de Sinalização NOD1/metabolismo , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/metabolismo , Receptores de Interleucina-8A/metabolismo , Receptores de Interleucina-8B/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Mucosa Bucal/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço
11.
Molecules ; 21(2): 136, 2016 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-26805809

RESUMO

The whole plant of Anisomeles ovata has been widely used in Taiwan for treating inflammation-related skin and liver diseases, however, the detailed pharmacology mechanisms have yet to be elucidated. In the present study, one of the major components, 5,6,4'-trihydroxy-7,3'-dimethoxyflavone (5-TDMF), was purified from a methanol extract of Anisomeles ovata. A pharmacological study of this compound suggests that 5-TDMF possesses potent free radical scavenging activity both in vitro and ex vivo. Furthermore, 5-TDMF reduces nitric oxide and pro-inflammatory cytokine production in LPC-treated RAW 264.7 cells through the attenuation of nitric oxide synthase and cyclooxygenase-2. Additional experiments suggest that of 5-TDMF interferes with nuclear factor-κB translocation and mitogen-activated protein kinase pathways. These results identify 5-TDMF as an anti-oxidant and anti-inflammatory compound, explain the pharmacologic function of Anisomeles ovata and suggest its great potential as a new anti-inflammatory remedy.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Flavonas/farmacologia , Lipopolissacarídeos/efeitos adversos , Macrófagos/efeitos dos fármacos , Animais , Ciclo-Oxigenase 2/metabolismo , Flavonas/isolamento & purificação , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Lamiaceae/química , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Células RAW 264.7
12.
Colloids Surf B Biointerfaces ; 116: 153-9, 2014 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-24469440

RESUMO

A simple and economic methodology to synthesize three types of novel dimeric cholesterol derivatives (DCDs) was developed. Results obtained from dynamic light scattering and transmission electron microscopy show that spherical and/or angular nano-structural aggregates of DCDs are formed by self-assembly in aqueous solution. The size and morphology of DCD dispersions depend on the spatial arrangement of the substituents and polarity of the head group in the DCD structures. The cytoxicity of DCD dispersions to human keratinocytes (HaCaT) and squamous cell carcinomas (SCC25) cells was also evaluated by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The present novel DCD dispersions were not toxic to HaCaT and SCC25 cells at appropriate tested concentrations.


Assuntos
Colesterol/síntese química , Sobrevivência Celular , Células Cultivadas , Colesterol/química , Dimerização , Humanos , Queratinócitos/citologia , Conformação Molecular , Tamanho da Partícula , Propriedades de Superfície
13.
BMC Complement Altern Med ; 13: 237, 2013 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-24070160

RESUMO

BACKGROUND: Alpinia oxyphylla is a common remedy in traditional Chinese medicine. Yakuchinone A is a major constituent of A. oxyphylla and exhibits anti-inflammatory, antitumor, antibacterial, and gastric protective activities. METHODS: Antioxidant and antitumor characteristics of yakuchinone A in skin cancer cells as well as novel mechanisms for the inhibition of adipocyte differentiation, cestocidal activities against Hymenolepis nana adults, and nematocidal activities against Anisakis simplex larvae are investigated. RESULTS: Yakuchinone A presents the ability of the removal of DPPH·and ABTS+ free radicals and inhibition of lipid peroxidation. Yakuchinone A suppresses intracellular lipid accumulation during adipocyte differentiation in 3 T3-L1 cells and the expressions of leptin and peroxisome proliferator-activated receptor γ (PPARγ). Yakuchinone A induces apoptosis and inhibits cell proliferation in skin cancer cells. The inhibition of cell growth by yakuchinone A is more significant for non-melanoma skin cancer (NMSC) cells than for melanoma (A375 and B16) and noncancerous (HaCaT and BNLCL2) cells. Treatment BCC cells with yakuchinone A shows down-regulation of Bcl-2, up-regulation of Bax, and an increase in cleavage poly (ADP-ribose) polymerase (PARP). This suggests that yakuchinone A induces BCC cells apoptosis through the Bcl-2-mediated signaling pathway. The anthelmintic activities of yakuchinone A for A. simplex are better than for H. nana. CONCLUSIONS: In this work, yakuchinone A exhibits antioxidative properties, anti-adipocyte differentiation, antitumor activity, and anthelmintic activities against A. simplex and H. nana.


Assuntos
Alpinia/química , Anti-Helmínticos/farmacologia , Antioxidantes/farmacologia , Diferenciação Celular/efeitos dos fármacos , Guaiacol/análogos & derivados , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Animais , Anisakis/efeitos dos fármacos , Anti-Helmínticos/química , Antioxidantes/química , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Guaiacol/química , Guaiacol/farmacologia , Humanos , Hymenolepis nana/efeitos dos fármacos , Larva/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos
14.
Artigo em Inglês | MEDLINE | ID: mdl-23554834

RESUMO

Brazilein, a natural, biologically active compound from Caesalpinia sappan L., has been shown to exhibit anti-inflammatory and antioxidant properties and to inhibit the growth of several cancer cells. This study verifies the antioxidant and antitumor characteristics of brazilein in skin cancer cells and is the first time to elucidate the inhibition mechanism of adipocyte differentiation, cestocidal activities against Hymenolepis nana, and reduction of spontaneous movement in Anisakis simplex. Brazilein exhibits an antioxidant capacity as well as the ability to scavenge DPPH(•) and ABTS(•+) free radicals and to inhibit lipid peroxidation. Brazilein inhibited intracellular lipid accumulation during adipocyte differentiation in 3T3-L1 cells and suppressed the induction of peroxisome proliferator-activated receptor γ (PPAR γ ), the master regulator of adipogenesis, suggesting that brazilein presents the antiobesity effects. The toxic effects of brazilein were evaluated in terms of cell viability, induction of apoptosis, and the activity of caspase-3 in BCC cells. The inhibition of the growth of skin cancer cells (A431, BCC, and SCC25) by brazilein is greater than that of human skin malignant melanoma (A375) cells, mouse leukemic monocyte macrophage (RAW 264.7 cells), and noncancerous cells (HaCaT and BNLCL2 cells). The anthelmintic activities of brazilein against Hymenolepis nana are better than those of Anisakis simplex.

15.
Biol Pharm Bull ; 35(12): 2198-203, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23207771

RESUMO

trans-Caffeic acid stearyl ester (TCASE) from the root cortex of Paeonia suffruticosa ANDREWS is a traditional medicinal herb that has several beneficial properties. However, the inhibitory effect of TCASE on melanogenesis has not been explored. In the cell viability assay, TCASE did not show a cytotoxic effect at a dose of 65 µM for 48 h in B16, HaCaT and Hs68 cells. TCASE considerably inhibits melanin synthesis, and reduces intracellular cyclic adenosine monophosphate (cAMP) levels, tyrosinase activity and L-3-(3,4-dihydroxyphenyl)-alanine (DOPA) oxidase activity in a concentration-dependent manner in the presence of α-melanocyte-stimulating hormone (α-MSH) in B16 cells, and the inhibition efficiency of TCASE exceeds that of ascorbic acid and arbutin. TCASE reduces melanocortin-1 receptor (MC1R), microphthalmia transcription factor (MITF), tyrosinase, tyrosinase-related protein-2 (TRP-2) and TRP-1 mRNA and protein levels in B16 cells. Based on the findings, TCASE is posited to inhibit melanogenesis signaling while suppressing cAMP levels and, subsequently, MC1R, MITF, tyrosinase, TRP-2 and TRP-1 down-regulation, resulting in the suppression of tyrosinase activity, DOPA oxidase activity and melanin synthesis.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Ácidos Cafeicos/uso terapêutico , Melaninas/biossíntese , Melanoma Experimental/tratamento farmacológico , Paeonia/química , Fitoterapia , alfa-MSH/metabolismo , Animais , Antineoplásicos Fitogênicos/farmacologia , Ácidos Cafeicos/farmacologia , Linhagem Celular Tumoral , AMP Cíclico/metabolismo , Regulação para Baixo , Humanos , Melanoma Experimental/metabolismo , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Transdução de Sinais
16.
J Agric Food Chem ; 60(31): 7690-6, 2012 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-22800339

RESUMO

4-(3,4-Dihydroxybenzoyloxymethyl)phenyl-O-ß-d-glucopyranoside (DBPG), a polyphenolic glycoside, isolated from Origanum vulgare has shown 1,1-diphenyl-2-picrylhydrazyl (DPPH(•))-scavenging capacity in previous work. This study demonstrated that DBPG exhibits antioxidant activity by a series of DPPH(•), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS(•+)), and superoxide anion radical (O(2)(•-)) radical-scavenging assays. The inhibition of lipid peroxidation (LP) by DBPG exceeded that by l-ascorbic acid (AA) in a liposome model system. Adding DBPG to mouse liver and brain tissue inhibited the formation of thiobarbituric acid reactive substances (TBARS) to a greater extent than did trolox. In the oxygen stress test, BNLCL2 and HaCaT cells pretreated with DBPG showed increased activities of glutathione peroxidase (GPx), perhaps as a result of reduction of the production of reactive oxygen species (ROS). These findings proved that DBPG had antioxidant activities and a cytoprotective effect in hepatocytes and keratinocytes, suggesting that DBPG may be a useful food and cosmetic additive.


Assuntos
Sequestradores de Radicais Livres/farmacologia , Metilglucosídeos/farmacologia , Origanum/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Linhagem Celular , Sequestradores de Radicais Livres/análise , Humanos , Metilglucosídeos/análise , Camundongos , Extratos Vegetais/análise
17.
Biochim Biophys Acta ; 1820(7): 1081-91, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22554915

RESUMO

BACKGROUND: Apigenin, a natural plant flavone, may have chemopreventive and therapeutic potentials for anti-inflammatory, antioxidant, and anti-cancer. Nevertheless, the anti-tumor effect of apigenin on human head and neck squamous cell carcinoma (HNSCC) is not fully understood. METHODS: The antioxidant capacity and protective effects of apigenin against oxidative stress in murine normal embryonic liver BNLCL2 cells are examined. Cell viability, morphologic change, clonogenic survival, cell cycle distribution, reactive oxygen species (ROS) production, glutathione formation, and death receptors- and Bcl-2-mediated caspase pathways of HNSCC SCC25 cells and A431 cells with apigenin are investigated. RESULTS: Apigenin inhibits the growth of SCC25 and A431 cells and induces cell cycle arrest in the G2/M phase. Apigenin has an antioxidant capacity as well as the ability to inhibit lipid peroxidation. It protects BNLCL2 cells against oxidative damage, and is potentially able to prevent cancer. Apigenin increases intracellular ROS levels and reduces levels of glutathione; it also induces cell apoptosis via tumor necrosis factor receptor (TNF-R)-, TNF-related apoptosis-inducing ligand receptor (TRAIL-R)-, and Bcl-2-mediated caspase-dependent cell death pathways in SCC25 cells. The combination of apigenin with 5-fluorouracil (5-Fu) or cisplatin induces the dramatic death of SCC25 cells. CONCLUSIONS: Apigenin induces SCC25 cell apoptosis via the up-regulation of both TNF-R and TRAIL-R signaling pathways, and has a synergistic effect on the inhibition of cell proliferation in combination with 5-Fu or cisplatin. GENERAL SIGNIFICANCE: These analytical findings suggest that apigenin may be a good therapeutic agent against HNSCC cells.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apigenina/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptores do Fator de Necrose Tumoral/metabolismo , Animais , Western Blotting , Carcinoma de Células Escamosas/metabolismo , Caspases/genética , Caspases/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cisplatino/administração & dosagem , Sinergismo Farmacológico , Citometria de Fluxo , Fluoruracila/administração & dosagem , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Melanoma/patologia , Camundongos , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/genética , Espécies Reativas de Oxigênio/metabolismo , Receptores do Fator de Necrose Tumoral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Ligante Indutor de Apoptose Relacionado a TNF/genética , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo
18.
Eur J Pharmacol ; 683(1-3): 1-9, 2012 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-22374256

RESUMO

Mdivi-1 is an inhibitor of dynamin related protein 1- (drp1)-mediated mitochondrial fission. However, the mechanisms through which this compound interacts directly with ion currents in heart cells remain unknown. In this study, its effects on ion currents and membrane potential in murine HL-1 cardiomyocytes were investigated. In whole-cell recordings, the addition of mdivi-1 decreased the amplitude of tail current (I(tail)) for the rapidly activating delayed-rectifier K⁺ current (I(Kr)) in a concentration-dependent manner with an IC50 value at 11.6 µM, a value that resembles the inhibition requirement for mitochondrial division. It shifted the activation curve of I(tail) to depolarized voltages with no change in the gating charge. However, mdivi-1 did not alter the rate of recovery from current inactivation. In cell-attached configuration, mdivi-1 inside the pipette suppressed the activity of acetylcholine-activated K⁺ channels without modifying the single-channel conductance. Mdivi-1 (30 µM) slightly depressed the peak amplitude of Na⁺ current with no change in the overall current-voltage relationship. Under current-clamp recordings, addition of mdivi-1 resulted in prolongation for the duration of action potentials (APs) and to increase the firing of spontaneous APs in HL-1 cells. Similarly, in pituitary GH3 cells, mdivi-1 was effective in directly suppressing the amplitude of ether-à-go-go-related gene-mediated K⁺ current. Therefore, the lengthening of AP duration and increased firing of APs caused by mdivi-1 can be primarily explained by its inhibition of these K⁺ channels enriched in heart cells. The observed effects of mdivi-1 on ion currents were direct and not associated with its inhibition of mitochondrial division.


Assuntos
Fenômenos Fisiológicos Celulares/efeitos dos fármacos , Canais de Potássio Éter-A-Go-Go/antagonistas & inibidores , Átrios do Coração/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias Cardíacas/efeitos dos fármacos , Bloqueadores dos Canais de Potássio/farmacologia , Quinazolinonas/farmacologia , Acetilcolina/antagonistas & inibidores , Acetilcolina/metabolismo , Animais , Linhagem Celular , Canais de Potássio de Retificação Tardia/antagonistas & inibidores , Canais de Potássio de Retificação Tardia/metabolismo , Dinaminas/antagonistas & inibidores , Canal de Potássio ERG1 , Canais de Potássio Éter-A-Go-Go/genética , Canais de Potássio Éter-A-Go-Go/metabolismo , Átrios do Coração/metabolismo , Camundongos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Concentração Osmolar , Técnicas de Patch-Clamp , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Interferência de RNA , RNA Interferente Pequeno , Ratos
19.
Biochim Biophys Acta ; 1820(7): 1149-57, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22348919

RESUMO

BACKGROUND: Skin cancers are reportedly increasing worldwide. Developing novel anti-skin cancer drugs with minimal side effects is necessary to address this public health issue. Sinuleptolide has been demonstrated to possess anti-cancer cell activities; however, the mechanisms underlying the anti-skin cancer effects of 5-epi-sinuleptolide and sinuleptolide remain poorly understood. METHODS: Apoptosis cell, cell-cycle-related regulatory factors, and mitochondria- and death receptor-dependent caspase pathway in 5-epi-sinuleptolide-induced cell apoptosis were examined using SCC25 cells. RESULTS: 5-epi-Sinuleptolide inhibited human skin cancer cell growth more than did sinuleptolide. Treatment of SCC25 cells with 5-epi-sinuleptolide increased apoptotic body formation, and induced cell-cycle arrest during the G2/M phase. Notably, 5-epi-sinuleptolide up-regulated p53 and p21 expression and inhibited G2/M phase regulators of cyclin B1 and cyclin-dependent kinease 1 (CDK1) in SCC25 cells. Additionally, 5-epi-sinuleptolide induced apoptosis by mitochondria-mediated cytochrome c and Bax up-expression, down-regulated Bcl-2, and activated caspase-9 and -3. 5-epi-Sinuleptolide also up-regulated tBid, which is associated with up-regulation of tumor necrosis factor-α (TNF-α) and Fas ligand (FasL) and their cognate receptors (i.e., TNF-RI, TNF-R2 and Fas), downstream adaptor TNF-R1-associated death domain (TRADD) and Fas-associated death domain (FADD), and activated caspase-8 in SCC25 cells. CONCLUSIONS: The analytical results indicate that the death receptor- and mitochondria-mediated caspase pathway is critical in 5-epi-sinuleptolide-induced apoptosis of skin cancer cells. GENERAL SIGNIFICANCE: This is the first report suggesting that the apoptosis mediates the anti-tumor effect of 5-epi-sinuleptolide. The results of this study might provide useful suggestions for designing of anti-tumor drugs for skin cancer patients.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/tratamento farmacológico , Caspases/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Diterpenos/farmacologia , Mitocôndrias/efeitos dos fármacos , Neoplasias Cutâneas/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo , Western Blotting , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Sobrevivência Celular/efeitos dos fármacos , Proteína Ligante Fas/metabolismo , Imunofluorescência , Humanos , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Ligante Indutor de Apoptose Relacionado a TNF/genética , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Células Tumorais Cultivadas
20.
Life Sci ; 89(19-20): 691-701, 2011 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-21925512

RESUMO

AIMS: PF573228 is an inhibitor of focal adhesion kinase (FAK) and recognized to affect cell adhesion and migration in many types of cells. Its effects on ion currents and membrane potential have been investigated in this study. MAIN METHOD: Electrophysiological studies of PF573228 actions on ion currents were performed in pituitary tumor (GH(3)) cells, in GH(3) cells transfected with K(Ca)1.1 siRNAs and in human embryonic kidney (HEK) cells expressing α-human slowpoke (α-hSlo). KEY FINDINGS: In whole-cell experiments, PF573228 reversibly increased the amplitude of Ca(2+)-activated K(+) currents (I(K(Ca))) in GH(3) cells. In inside-out recordings, this compound added to the bath did not modify single-channel conductance but stimulated large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels with an EC(50) value of 3.2 µM. As BK(Ca)-channel activity was stimulated by PF573228 (3 µM), subsequent application of BMS191011 (3 µM) did not further increase channel activity. PF573228 shifted the activation curve of BK(Ca) channels to less positive membrane potential. Change in the kinetic behavior of BK(Ca) channels caused by this compound is a result of the increased backward rate constants between closed states. PF573228 depressed the firing of action potentials in GH(3) cells. However, in GH(3) cells transfected with K(Ca)1.1 siRNAs, PF573228-stimulated I(K(Ca)) was abolished. In HEK293T cells expressing α-hSlo, PF573228 enhanced BK(Ca)-channel activity. SIGNIFICANCE: In addition to an inhibition of FAK phosphorylation, PF573228 is effective in activating BK(Ca) channels. The direct stimulation of these channels by this compound may contribute to the underlying mechanism through which it influences cell behavior.


Assuntos
Proteína-Tirosina Quinases de Adesão Focal/antagonistas & inibidores , Canais de Potássio Ativados por Cálcio de Condutância Alta/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , Quinolonas/farmacologia , Sulfonas/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Células HEK293 , Humanos , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Fosforilação/efeitos dos fármacos , Neoplasias Hipofisárias/patologia , Ratos , Transfecção
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