RESUMO
Ceramide plays an important role in maintaining the skin barrier function. Aging and atopic dermatitis are known to reduce the levels of ceramide. Application of exogenous ceramide to the skin can restore the barrier function. In recent years, the effect of oral intake of ceramide has been demonstrated to improve the skin barrier function, and it has been marketed as a food supplement. Therefore, it is important to provide information on the safety of unintentional overdose of ceramide. This randomized, double-blind, placebo-controlled study was conducted in 30 healthy adults, aged between 20 and 60 years of age (both female and male). The subjects consumed either dietary supplement, comprising 1197 mg of acetic acid bacteria containing 9.06 mg of ceramide, or placebo for four consecutive weeks. Safety was evaluated based on physical measurements, blood test, urinalysis, adverse events, and side effects. The results showed several significant differences in physical measures and blood tests between the two groups. However, these differences were considered to be unrelated to the intake of the ceramide-containing acetic acid bacteria or placebo. Thus, no adverse effects or clinically concerning changes in physical, blood, and urine parameters were observed due to the excessive intake of the ceramide-containing acetic acid bacteria in the present study.TRIAL REGISTRATION: UMIN000035481.
Assuntos
Ácido Acético , Bactérias , Ceramidas/administração & dosagem , Suplementos Nutricionais , Administração Oral , Adulto , Ceramidas/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Segurança , Fenômenos Fisiológicos da Pele , Fatores de Tempo , Adulto JovemRESUMO
The barrier function of the skin protects it from external stresses to which it is constantly exposed, such as dryness, ultraviolet rays, and chemicals. Lipids, in particular a type of sphingolipid known as ceramides, play a central role in the barrier function of the skin by preventing dryness. The number of ceramides in the skin is known to decrease with age, which has led to the development of a large number of anti-aging cosmetic products that contain ceramides. Recently, it has become evident that oral intake of ceramides can also improve the quality of the skin. To elucidate the effects of oral ceramide intake on skin moisture content, we conducted a randomized, double-blinded, placebo-controlled parallel comparative study in which males and females between 20 and 60 years of age who were worried about dry skin ingested a food with acetic acid bacteria containing 0.8 mg of dihydroceramide or a placebo for 12 weeks. Concurrently, we investigated the safety of continuous ingestion of the ceramide-containing food over 12 weeks. Oral intake of ceramide over the 12 weeks significantly improved stratum corneum hydration, i.e. the moisture content of the skin, and did not result in harmful effects in any of the participants.
Assuntos
Acetobacter , Água Corporal/metabolismo , Ceramidas/administração & dosagem , Epiderme/metabolismo , Estado de Hidratação do Organismo/efeitos dos fármacos , Pele/metabolismo , Administração Oral , Adulto , Ceramidas/farmacologia , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Envelhecimento da Pele/efeitos dos fármacos , Adulto JovemRESUMO
Ceramides have several well-known biological properties, including anti-pigmentation and anti-melanogenesis, which make them applicable for use in skincare products in cosmetics. However, the efficacy of ceramides is still limited. Dermal or transdermal drug delivery systems can enhance the anti-pigmentation properties of ceramides, although there is currently no systemic evaluation method for the efficacy of these systems. Here we prepared several types of lecithin-based emulsion of maize-derived glucosylceramide, determining PC70-ceramide (phosphatidylcholine-base) to be the safest and most effective anti-pigmentation agent using zebrafish larvae. We also demonstrated the efficacy of PC70 as a drug delivery system by showing that PC70-Nile Red (red fluorescence) promoted Nile Red accumulation in the larval bodies. In addition, PC70-ceramide suppressed melanin in mouse B16 melanoma cells compared to ceramide alone. In conclusion, we developed a lecithin-based dermal delivery method for ceramide using zebrafish larvae with implications for human clinical use.
Assuntos
Ceramidas/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Lecitinas/química , Pigmentação/efeitos dos fármacos , Zea mays/química , Animais , Ceramidas/química , Melanoma Experimental , Camundongos , Pigmentação da Pele/efeitos dos fármacos , Peixe-ZebraRESUMO
BACKGROUND: Skin moisturizing is advocated to take care of the skin of patients with atopic dermatitis (AD). However, many patients stop using moisturizers in the summer because of excessive sweating and high humidity. OBJECTIVES: To examine the efficacy of a moisturizing gel containing a pseudo-ceramide and a eucalyptus extract, which enhances epidermal ceramide synthesis of patients with mild AD in the summer. METHODS: We performed a single-blinded 4-week clinical trial of body care on 44 Japanese subjects who had mild AD. They had not applied any moisturizer on their body in the summer. Twenty-seven subjects used the moisturizing gel containing a pseudo-ceramide and a eucalyptus extract twice a day and the 17 other subjects did not use any moisturizer. Prior to and at the end of weeks 2 and 4, the skin conditions of each subject were evaluated. RESULTS: During the test period, the atmospheric temperature increased and skin dryness and scaling significantly improved with or without application of the moisturizing gel. However, the improvement in dryness of the treated group was significantly higher than that of the nontreated group. Erythema and itchiness were significantly improved only in the treated group. The skin hydration on the forearm increased significantly only in the treated group. Accompanying those improvements, the quality of life of the subjects, evaluated by Skindex-16® , was significantly improved. CONCLUSION: The usage of a moisturizer containing a pseudo-ceramide and a eucalyptus extract is effective for care of the skin of AD subjects even in the summer.
Assuntos
Ceramidas/administração & dosagem , Dermatite Atópica/tratamento farmacológico , Emolientes/administração & dosagem , Eucalyptus/química , Extratos Vegetais/administração & dosagem , Adulto , Povo Asiático , Ceramidas/química , Emolientes/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estações do Ano , Método Simples-Cego , Pele/efeitos dos fármacos , Resultado do TratamentoRESUMO
Combination therapy is one of the important methods to improve therapeutic effect on the treatment of hepatocellular carcinoma (HCC). Sorafenib (SF) is a canonical US Food and Drug Administration-approved multikinase molecule inhibitor against HCC. However, therapeutic benefit with Sorafenib alone was usually unsatisfactory. Ceramide (CE) is an endogenous bioactive sphingolipid, which has a strong potential to suppress various tumors. The combination of SF and CE was hoping to exert maximum synergistic antitumor effect through different tumor-suppressible mechanisms. In this respect, SF and CE co-loaded liposomes (SF/CE-liposomes) were developed to verify synergistic antitumor efficacy. The optimal molar ratio of SF and CE was determined through combination index. SF/CE-liposomes were prepared by thin-film hydration method, which exhibited spherical or ellipsoidal shape. Particle size of SF/CE-liposomes was 174 ± 4 nm with homogeneous distribution. Release profile of SF demonstrated that addition of CE imposed no significant impact on the release of SF. SF/CE-liposomes exhibited acceptable stability in different media and desirable storage stability over 30 days at 4°C. In vitro cellular uptake confirmed that SF/CE-liposomes could be efficiently internalized into HepG2 cells. In vitro cytotoxicity evaluation indicated that SF/CE-liposomes exhibited higher cytotoxicity on HepG2 cells. IC50 value of SF/CE-liposomes was 11.5 ± 0.44 µM, which was significantly lower than that of SF-liposomes (**p < 0.01). Evaluation of in vivo synergistic effect on H22-bearing mice verified that SF/CE-liposomes achieved robust antitumor activity in preventing tumor growth. All results suggested that SF/CE-liposomes might be served as an efficient co-delivery system for improving therapeutic efficacy of HCC.
Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Ceramidas/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Animais , Antineoplásicos/metabolismo , Carcinoma Hepatocelular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Ceramidas/metabolismo , Sinergismo Farmacológico , Feminino , Células Hep G2 , Humanos , Lipossomos , Neoplasias Hepáticas/metabolismo , Camundongos , Niacinamida/administração & dosagem , Niacinamida/metabolismo , Tamanho da Partícula , Compostos de Fenilureia/metabolismo , Sorafenibe , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/fisiologiaRESUMO
Deficiency or altered composition of stratum corneum (SC) lipids such as ceramides (CERs), causing skin barrier dysfunction and skin dryness, have been associated with skin diseases such as atopic dermatitis and psoriasis, and ageing. Replenishing the depleted native CERs with exogenous CERs has also been shown to have beneficial effects in restoring the skin barrier. Phyto-derived CERs such as oat CERs were shown to be potential for skin barrier reinforcement. To effect this, however, the oat CERs should overcome the SC barrier and delivered deep into the lipid matrix using the various novel formulations. In an attempt to demonstrate the potential use of oat CERs, lecithin-based microemulsions (MEs) and starch-based nanoparticles (NPs) were formulated and characterized. Besides, ME gel and NP gel were also prepared using Carbopol®980 as a gelling agent. The in vitro release and penetration (using artificial four-layer membrane system) and ex vivo permeation (using excised human skin) of oat CERs from the various formulations were investigated. The results revealed ME enhanced the in vitro release and penetration oat CERs compared to the other formulations. On the other hand, the NPs retarded the release of oat CERs and small quantities of oat CERs incorporated into NP gel penetrated into the deeper layers of the multilayer membranes. The penetration-enhancing effect of ME was also observed in the ex vivo permeation studies where significant quantities of oat CERs were found in the acceptor compartment. Compared to the ME, the ME gel exhibited reduced depth and extent of oat CERs permeation. As compared to NP gel, ME gel enhanced the degree of permeation of oat CERs into the deeper layer of the skin. Generally the gel formulations were effective in concentrating oat CERs in the SC where they are needed to be.
Assuntos
Avena/química , Ceramidas/administração & dosagem , Ceramidas/química , Nanopartículas/química , Pele/efeitos dos fármacos , Química Farmacêutica/métodos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Humanos , Lecitinas/química , Lipídeos/química , Permeabilidade/efeitos dos fármacos , Absorção Cutânea/efeitos dos fármacos , Dermatopatias/tratamento farmacológicoRESUMO
Ceramide 2-aminoethylphosphonate (CAEP), a sphingophosphonolipid containing a carbon-phosphorus bond, is frequently found in marine organisms and has a unique triene type of sphingoid base in its structure. CAEP has not been evaluated as a food ingredient, although it is generally contained in Mollusca organisms such as squids and shellfish, which are consumed worldwide. In this study, we aimed to elucidate the effects of CAEP as a food component by evaluating the digestion of CAEP extracted from the skin of the jumbo flying squid Dosidicus gigas. Our results revealed that dietary CAEP was digested to free sphingoid bases via ceramides by the mouse small intestinal mucosa. At pH 7.2, CAEP was hydrolyzed more rapidly than the major mammalian sphingolipid sphingomyelin; however, the hydrolysis of CAEP was similar to that of sphingomyelin at pH 9.0. Thus, the digestion of CAEP may be catalyzed by alkaline spingomyelinase and other enzymes. Our findings provide important insights into the digestion of the dietary sphingophosphonolipid CAEP in marine foods.
Assuntos
Ácido Aminoetilfosfônico/análogos & derivados , Ceramidas/administração & dosagem , Decapodiformes/química , Intestino Delgado/metabolismo , Ácido Aminoetilfosfônico/administração & dosagem , Ácido Aminoetilfosfônico/farmacologia , Animais , Ceramidas/farmacologia , Suplementos Nutricionais , Hidrólise , Camundongos , Esfingomielina Fosfodiesterase/metabolismo , Esfingomielinas/químicaRESUMO
The objective of our study was to determine the mechanism of action of the short-chain ceramide analog, C6-ceramide, and the breast cancer drug, tamoxifen, which we show coactively depress viability and induce apoptosis in human acute myelogenous leukemia cells. Exposure to the C6-ceramide-tamoxifen combination elicited decreases in mitochondrial membrane potential and complex I respiration, increases in reactive oxygen species (ROS), and release of mitochondrial proapoptotic proteins. Decreases in ATP levels, reduced glycolytic capacity, and reduced expression of inhibitors of apoptosis proteins also resulted. Cytotoxicity of the drug combination was mitigated by exposure to antioxidant. Cells metabolized C6-ceramide by glycosylation and hydrolysis, the latter leading to increases in long-chain ceramides. Tamoxifen potently blocked glycosylation of C6-ceramide and long-chain ceramides. N-desmethyltamoxifen, a poor antiestrogen and the major tamoxifen metabolite in humans, was also effective with C6-ceramide, indicating that traditional antiestrogen pathways are not involved in cellular responses. We conclude that cell death is driven by mitochondrial targeting and ROS generation and that tamoxifen enhances the ceramide effect by blocking its metabolism. As depletion of ATP and targeting the "Warburg effect" represent dynamic metabolic insult, this ceramide-containing combination may be of utility in the treatment of leukemia and other cancers.
Assuntos
Ceramidas/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Tamoxifeno/administração & dosagem , Trifosfato de Adenosina/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sinergismo Farmacológico , Complexo I de Transporte de Elétrons/efeitos dos fármacos , Humanos , Leucemia Mieloide Aguda/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
The aim of this study was to investigate the effect of Douxo(®) Calm Mousse (Sogeval, Laval, France) on restoration of the skin barrier in a canine model of barrier disruption. Tape strips were performed, daily for 6 days, on the lateral thorax of five healthy beagle dogs. Douxo(®) Calm Mousse was applied daily for 5 days to one side of the thorax and the opposite side was left untreated. The effects of treatment were evaluated by measurement of transepidermal water loss (TEWL) and pH and by histological assessment of disrupted skin at various times during barrier repair. Although no effect on TEWL was observed, Douxo(®) Calm Mousse maintained an acidic pH after three applications and reduced skin inflammation, which was most pronounced after five applications. The results of the study suggest that Douxo(®) Calm Mousse exerts a beneficial effect on barrier restoration and on markers of inflammation.
Assuntos
Anti-Inflamatórios/administração & dosagem , Pele/efeitos dos fármacos , Administração Tópica , Animais , Ceramidas/administração & dosagem , Modelos Animais de Doenças , Cães , Emulsões/administração & dosagem , Concentração de Íons de Hidrogênio , Inflamação/patologia , Óleos de Plantas/administração & dosagem , Pele/lesões , Pele/patologia , Esfingosina/administração & dosagem , Esfingosina/análogos & derivados , ortoaminobenzoatos/administração & dosagemRESUMO
Several skin diseases such as psoriasis and atopic dermatitis are associated with the depletion or disturbance of stratum corneum (SC) lipids such as ceramides (CERs), free fatty acids and cholesterol. Studies suggested that replenishment of these lipids might help to treat diseased, affected or aged skin. With this premises in mind, there are some formulations in the market that contain SC lipids and currently, to facilitate permeation of the lipids deep into the SC, various CERs, and other SC lipid microemulsions (MEs) were developed and characterised using lecithin or TEGO® CARE PL 4 (TCPL4) as base surfactants. However, to date, there are no reports that involve the permeability of SC lipids into and across the SC, and therefore, the penetration of CER [NP] as a model ceramide from various formulations was investigated ex vivo using Franz diffusion cell. Besides, the toxicity of the MEs was assessed using hen's egg test chorioallantoic membrane (HET-CAM). The results of the study showed that CER [NP] could not permeate into deeper layers of the SC from a conventional hydrophilic cream. Unlike the cream, CER [NP] permeated into the deeper layers of the SC from both type of MEs, where permeation of the CER was more and into deeper layers from droplet type and lecithin-based MEs than bicontinuous (BC) type and TCPL4 based MEs, respectively. The CER also permeated into deeper layers from ME gels which was, however, shallow and to a lesser extent when compared with the MEs. The results of HET-CAM showed that both MEs are safe to be used topically, with lecithin-based MEs exhibiting better safety profiles than TCPL4 based MEs. Concluding, the study showed that the MEs are safe to be used on the skin for the controlled penetration of CER [NP] deep into the SC.
Assuntos
Ceramidas/química , Ceramidas/metabolismo , Preparações de Ação Retardada/química , Preparações de Ação Retardada/metabolismo , Emulsões/química , Emulsões/metabolismo , Pele/metabolismo , Animais , Ceramidas/administração & dosagem , Química Farmacêutica/métodos , Galinhas , Preparações de Ação Retardada/administração & dosagem , Difusão , Ovos , Emulsões/administração & dosagem , Humanos , Lecitinas/administração & dosagem , Lecitinas/química , Lecitinas/metabolismo , Lipídeos/administração & dosagem , Lipídeos/química , PermeabilidadeRESUMO
PURPOSE: To improve the solubility and penetration of Ceramide AP (CER [AP]) into the stratum corneum that potentially restores the barrier function of aged and affected skin. METHODS: CER [AP] microemulsions (MEs) were formulated using lecithin, Miglyol® 812 (miglyol) and water-1,2 pentandiol (PeG) mixture as amphiphilic, oily and hydrophilic components, respectively. The nanostructure of the MEs was revealed using electrical conductivity, differential scanning calorimeter (DSC) and electron paramagnetic resonance (EPR) techniques. Photon correlation spectroscopy (PCS) was used to measure the sizes and shape of ME droplets. The release and penetration of the CER into the stratum corneum was investigated in vitro using a multi-layer membrane model. RESULTS: The MEs exhibited excellent thermodynamic stability (>2 years) and loading capacity (0.5% CER [AP]). The pseudo-ternary phase diagrams of the MEs were obtained and PCS results showed that the droplets are spherical in shape and bigger in size. In vitro investigations showed that the MEs exhibited excellent rate and extent of release and penetration. CONCLUSIONS: Stable lecithin-based CER [AP] MEs that significantly enhance the solubility and penetration of CER [AP] into the stratum corneum were developed. The MEs also have better properties than the previously reported polyglycerol fatty acid surfactant-based CER [AP] MEs.
Assuntos
Ceramidas/administração & dosagem , Sistemas de Liberação de Medicamentos , Emulsões/química , Epiderme/metabolismo , Lecitinas/química , Ceramidas/farmacocinética , Condutividade Elétrica , Humanos , Membranas Artificiais , Tamanho da Partícula , Refratometria , ViscosidadeRESUMO
BACKGROUND: Atopic dermatitis (AD) is a prevalent skin disorder with significant cost of treatment. Several prescription device moisturizers have been approved by the FDA to treat AD but are significantly more expensive than well-crafted over-the-counter (OTC) moisturizers. No studies have been performed to compare both the clinical efficacy and cost-efficacy of these prescription devices to OTC moisturizers. PURPOSE: The purpose of this study is to compare the clinical efficacy and cost-efficacy of a glycyrrhetinic acid-containing barrier repair cream (BRC-Gly, Atopiclair®), a ceramide-dominant barrier repair cream (BRC-Cer, EpiCeram®) and an OTC petroleum-based skin protectant moisturizer (OTC-Pet, Aquaphor Healing Ointment®) as monotherapy for mild-to-moderate AD in children. METHODS: Thirty-nine patients, age 2-17 years, with mild-to-moderate AD were randomized 1:1:1 to receive one of three treatments-BRC-Gly, BRC-Cer or OTC-Pet-with instructions to apply the treatment three times daily for three weeks. Disease severity and improvement was assessed at baseline and on days 7 and 21. RESULTS: No statistically significant difference for any efficacy assessment was found between the three groups at each time point. The OTC-Pet was found to be at least 47 times more cost-effective than BRC-Gly or BRC-Cer. LIMITATIONS: The relatively small sample size of 39 subjects was not sufficient to establish OTC-Pet as superior treatment in AD. CONCLUSIONS: OTC-Pet is as effective in treating mild-to-moderate AD as both BRC-Gly and BRC-Cer and is at least 47 times more cost-effective. NAME OF REGISTRY: II-AF-ATD-Aquaphor, Comparing the Efficacy and Cost-Effectiveness of Aquaphor to Atopiclair and EpiCeram in Children with Mild to Moderate Atopic Dermatitis. REGISTRATION IDENTIFIER: NCT01093469.
Assuntos
Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Emolientes/uso terapêutico , Administração Cutânea , Adolescente , Ceramidas/administração & dosagem , Ceramidas/economia , Ceramidas/uso terapêutico , Criança , Pré-Escolar , Colesterol/administração & dosagem , Colesterol/economia , Colesterol/uso terapêutico , Análise Custo-Benefício , Dermatite Atópica/patologia , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/economia , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/economia , Gorduras na Dieta/uso terapêutico , Método Duplo-Cego , Combinação de Medicamentos , Emolientes/administração & dosagem , Emolientes/economia , Ácidos Graxos/administração & dosagem , Ácidos Graxos/economia , Ácidos Graxos/uso terapêutico , Feminino , Ácido Glicirretínico/administração & dosagem , Ácido Glicirretínico/economia , Ácido Glicirretínico/uso terapêutico , Humanos , Masculino , Medicamentos sem Prescrição/administração & dosagem , Medicamentos sem Prescrição/economia , Medicamentos sem Prescrição/uso terapêutico , Vaselina/administração & dosagem , Vaselina/economia , Vaselina/uso terapêutico , Extratos Vegetais/administração & dosagem , Extratos Vegetais/economia , Extratos Vegetais/uso terapêutico , Medicamentos sob Prescrição/administração & dosagem , Medicamentos sob Prescrição/economia , Medicamentos sob Prescrição/uso terapêutico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Ceramides, specific lipid components of the skin, represent 35-40% of the intercellular cement binding cells together and contributing to skin hydration. A wheat extract rich in ceramides and digalactosyl-diglycerides was developed by Hitex in two forms: wheat extract oil (WEO) and wheat extract powder (WEP). In vitro tests and two clinical studies demonstrated promising efficacy results with WEP on skin hydration. To confirm these early results, a double-blind, randomized, placebo-controlled study was carried out on 51 women aged 20-63 years with dry to very dry skin who received either 350 mg of WEO or placebo for 3 months. Evaluation of skin hydration on legs, arms and face, assessed at baseline (D0) and at study end (D84) was performed by the dermatologist using dermatological scores (dryness, roughness, erythema), skin hydration measurement (corneometry) and self-assessment scores (Visual Analogue Scale: VAS). Perceived efficacy was noted by participants throughout the study; tolerability and overall acceptability of the study products were evaluated by the dermatologist and the participants at the end of study. Skin hydration was significantly increased between D0 and D84 on the arms (P < 0.001) and legs (P = 0.012) in the WEO group compared with placebo. Even if no significant statistical differences between groups were observed for the dermatological evaluation, skin dryness and redness tended to be reduced in the WEO group. Moreover, from D0 to D84, the VAS index had a tendency to increase in favour of WEO for the overall skin hydration (P = 0.084) indicating that participants perceived an improvement. The WEO capsules were perceived by participants as being more effective than placebo on all skin dryness signs. In conclusion, WEO capsules were well tolerated and appreciated. After 3 months' treatment, a significant increase in skin hydration and an improvement in associated clinical signs were observed in women with dry skin.
Assuntos
Ceramidas/administração & dosagem , Extratos Vegetais/administração & dosagem , Pele/efeitos dos fármacos , Triticum/química , Adulto , Método Duplo-Cego , Impedância Elétrica , Feminino , Humanos , Pessoa de Meia-Idade , Satisfação do Paciente , Projetos Piloto , Pele/química , Pele/metabolismo , Adulto JovemRESUMO
Ceramide signaling plays an important role in tumor progression and development of chemoresistance, and ceramide-based therapies are proposed as potential therapeutic tools for the treatment of breast cancer. We investigated the effect of exogenous ceramide on the cell cycle progression of MCF-7 breast cancer cells. Ceramide induced a selective arrest of MCF-7 cells in the G1-phase, which was associated with a decreased expression of cyclins D and E and increased expression of p53 and p21. Interestingly, inhibition of p53 using pifithrin alpha or RNAi sensitized MCF-7 cells to ceramide-induced cell death. DNA content analysis suggested that sensitization of cells was due to an increased induction of apoptosis in MCF-7 cells. The increased sensitivity to ceramide, in the context of p53 inhibition, may be due to decreased expression of p21, as siRNA targeted to p21 also sensitized MCF-7 cells to ceramide-induced death. These data demonstrate that in tumors with inactivating mutations of p53, ceramide-based therapies might provide a novel and effective treatment option.
Assuntos
Benzotiazóis/farmacologia , Neoplasias da Mama/patologia , Carcinoma/patologia , Ceramidas/farmacologia , RNA Interferente Pequeno/farmacologia , Tolueno/análogos & derivados , Proteína Supressora de Tumor p53/antagonistas & inibidores , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Benzotiazóis/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Carcinoma/tratamento farmacológico , Carcinoma/genética , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Ceramidas/administração & dosagem , Ciclina D/genética , Ciclina E/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , RNA Interferente Pequeno/administração & dosagem , Tolueno/administração & dosagem , Tolueno/farmacologia , Proteína Supressora de Tumor p53/genéticaRESUMO
Various detergents are used as skin cleansing products. In some cases, skin cleanser removes not only dirt but also valuable skin lipids. Therefore, detergents may disrupt epidermal barrier function despite that using of detergents are required for good skin hygiene. Lipid supplements can reverse detergent-induced dysfunction of the skin barrier. Elevated transepidermal water loss (TEWL) and riboflavin penetration in 5% SLS-treated rat and human skin were reversed by supplementation of monoglyceride (MG), squalene (SQ), cholesterol ester (CE) and pseudo-ceramide (Cer2). MG and Cer2 achieved the best results. MG appears to inhibit elution of intercellular ceramides, since more ceramides remained when the detergent was supplemented with MG. Topical application of Cer2 is not effective for recovery from artificially induced barrier disruption, but supplemented Cer2 into skin cleanser has a beneficial effect for prevention of detergent-induced barrier disruption. In conclusion, the prevention of barrier disruption is most important matter for maintaining skin health and barrier function. Therefore, we think that Cer2-supplemented skin cleanser is useful for conservation of skin barrier function.