RESUMO
Cinnamomum cassia possesses antioxidative activity and induces the apoptotic properties of various cancer types. However, its effect on osteosarcoma invasion and cancer stemness remains ambiguous. Here, we examined the molecular evidence of the anti-invasive effects of ethanoic C. cassia extracts (CCE). Invasion and migration were obviously suppressed after the expression of urokinase-type plasminogen activator and matrix metalloprotein 2 in human osteosarcoma 143B cells were downregulated. CCE reversed epithelial-to-mesenchymal transition (EMT) induced by transforming growth factor ß1 and downregulated mesenchymal markers, such as snail-1 and RhoA. CCE suppressed self-renewal property and the expression of stemness genes (aldehyde dehydrogenase, Nanog, and CD44) in the 143B cells. CCE suppressed cell viability, reduced the colony formation of osteosarcoma cancer cells, and induced apoptotic cell death in the 143B cells, as indicated by caspase-9 activation. The xenograft tumor model of immunodeficient BALB/c nude mice showed that CCE administered in vivo through oral gavage inhibited the growth of implanted 143B cells. These findings indicated that CCE inhibited the invasion, migration, and cancer stemness of the 143B cells. CCE reduced proliferation of 143B cell possibly because of the activation of caspase-9 and the consequent apoptosis, suggesting that CCE is a potential anticancer supplement for osteosarcoma.
Assuntos
Neoplasias Ósseas , Cinnamomum aromaticum , Osteossarcoma , Animais , Apoptose , Neoplasias Ósseas/patologia , Caspase 9/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Humanos , Camundongos , Camundongos Nus , Osteossarcoma/patologia , Extratos Vegetais/farmacologiaRESUMO
BACKGROUND: Substance abuse among young people has become a serious public health problem for years. The risk of relapse among illicit drug use is essential for developing adequate substance reuse prevention policies. The purpose of the current study is to investigate the potential predictor in long-term relapse rates among young patients that underwent a family-based treatment program. METHODS: To perform this study, 103 young patients with substance use (mean age: 16.2 years, 78.6% male) were referred to participate in a 10-week family-based treatment program. At the beginning and at the end of the treatment, the patients were required to fill out the Chinese Craving Beliefs Questionnaire (CCBQ), the Adolescents' Behavior-problem Scale (ABS), and the Family APGAR. Furthermore, the patients' caregivers had to fill out the Family APGAR, the 12-item version of the Chinese Health Questionnaire (CHQ), and the Parenting Stress Index (PSI). All patients were followed up for 5 years in order to observe their long-term outcomes regarding substance use relapse. RESULTS: During the 10-week family-oriented programs, the CCBQ scores, the CHQ scores and the Child-domain of PSI significantly decreased. Better changes in patients' behavioral problems during the treatment program predicted a lesser likelihood of substance use relapse in the subsequent 5 years. Furthermore, methamphetamine or 3,4-methylenedioxy-methamphetamine use and living in single-parent families were two factors associated with higher relapse rates. CONCLUSIONS: The changes in patients' behavioral problems during the treatment program may serve as a predictor of substance use relapse over the subsequent 5 years. This study's findings provide insight about substance use prevention and serve as a reference for policy-making.
RESUMO
Cinnamomum cassia exhibits antioxidative, apoptotic, and cytostatic properties. These activities have been attributed to the modulation of several biological processes and are beneficial for possible pharmaceutical applications. However, the potential of C. cassia in retarding lung adenocarcinoma cells metastasis remains ambiguous. We determined whether C. cassia extract (CCE) reduces metastasis of human lung adenocarcinoma cells. The results showed that CCE treatment (up to 60 µg/mL) for 24 h exhibited no cytotoxicity on the A549 and H1299 cell lines but inhibited the motility, invasiveness, and migration of these cells by repressing matrix metalloproteinase (MMP)-2 and urokinase-type plasminogen activator (u-PA). CCE also impaired cell adhesion to collagen. CCE significantly reduced p-focal adhesion kinase (FAK) Tyr397, p-FAK Tyr925, p-extracellular signal-regulated kinases (ERK)1/2, and Ras homolog gene family (Rho)A expression. CCE showed anti-metastatic activity of A549 and H1299 cells by repressing u-PA/MMP-2 via FAK to ERK1/2 pathways. These findings may facilitate future clinical trials of lung adenocarcinoma chemotherapy to confirm the promising results.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Cinnamomum aromaticum/química , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Extratos Vegetais/farmacologia , Células A549 , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Colágeno , Quinase 1 de Adesão Focal/metabolismo , Gelatina , Humanos , Neoplasias Pulmonares/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinase 2 da Matriz , Fosforilação/efeitos dos fármacos , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismoRESUMO
Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults and the major cause of mortality in urological cancer. Most patients with RCC are asymptomatic until the disease is advanced and unresectable. In this situation, systemic therapy with immunotherapy or molecularly targeted therapy agents play an important role in therapeutic strategy. Everolimus (EVE), an m-TOR inhibitor, has the potential to inhibit tumor progression at multiple levels and is indicated for the treatment of advanced RCC in patients whose disease has metastasis. In this study, we provide molecular evidence associated with the antimetastatic effect of everolimus by demonstrating the suppression of lung metastasis of 786-O cells in mouse model. This effect was associated with reduced protein expressions of p-FAK (Tyr 925), p-Src (Tyr416), Vimentin, and RhoA and also with increased the E-cadherin protein expression. In summary, these findings provide new insights into the molecular mechanisms involved in the antimetastatic effect of everolimus and are thus valuable in the treatment of metastatic RCC.
Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Renais/tratamento farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Everolimo/farmacologia , Proteína-Tirosina Quinases de Adesão Focal/antagonistas & inibidores , Neoplasias Renais/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Animais , Antineoplásicos/uso terapêutico , Caderinas/metabolismo , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/secundário , Linhagem Celular Tumoral , Everolimo/uso terapêutico , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Humanos , Neoplasias Renais/patologia , Neoplasias Pulmonares/secundário , Masculino , Camundongos , Fosforilação , Vimentina/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismoRESUMO
Metastasis is the most common cause of cancer-related mortality in patients, and epithelial-mesenchymal transition (EMT) is essential for cancer metastasis and antidrug resistance. Cinnamomum cassia has several antioxidative, anti-inflammatory, and anticancer biological effects. However, the anti-EMT effect of C. cassia in human lung carcinoma is rarely reported. In this study, we determined whether C. cassia extracts (CCE) reduces the EMT and tumor growth of human lung adenocarcinoma cells. CCE inhibited the transforming growth factor (TGF)-ß1-induced cell motility and invasiveness of A549 and H1299 cells by repressing matrix metalloproteinase-2 and urokinase-type plasminogen activator as well as impaired cell adhesion to collagen. CCE also affected the TGF-ß1-induced EMT by downregulating the expression of vimentin and fibronectin and upregulating E-cadherin. The nude mice xenograft model showed that CCE reduced A549 tumor growth. Thus, CCE possesses antimetastatic activity of A549 and H1299 cells by affecting EMT and suppressing A549 tumor growth in vivo. This result suggested that CCE could be used as an antimetastatic agent or as an adjuvant for anticancer therapy.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Fitogênicos/farmacologia , Cinnamomum aromaticum/química , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Extratos Vegetais/farmacologia , Fator de Crescimento Transformador beta1/farmacologia , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Caderinas/metabolismo , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Fibronectinas/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Metaloproteinase 2 da Matriz/metabolismo , Camundongos Nus , Transplante de Neoplasias , Extratos Vegetais/uso terapêutico , Ativador de Plasminogênio Tipo Uroquinase/metabolismoRESUMO
Epithelial-mesenchymal transition (EMT) is a process through which epithelial cells are transformed into mesenchymal cells; EMT diminishes cell polarity and cell-cell adhesion in cancer cells, leading to enhanced migratory and invasive properties. In this experiment, zymography, cell invasion, and migration assays were performed. Results indicated that Duchesnea indica extracts (DIE) inhibited highly metastatic A549 and H1299 cells by reducing the secretions of matrix metalloproteinase-2 and urokinase-type plasminogen activator. Cell adhesion assay also demonstrated that DIE reduced the cell adhesion properties. Western blot analysis showed that DIE down-regulated the expression of N-cadherin, fibronectin, and vimentin, which are mesenchymal markers, and enhanced that of E-cadherin, which is an epithelial marker. In vivo study showed that tumor growth was significantly reduced in BALB/c nude mouse xenograft model administered with oral gavage of DIE. Therefore, DIE could be exhibits potential as a phytochemical-based platform for prevention and treatment of lung cancer. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 2053-2063, 2017.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Fitogênicos/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Extratos Vegetais/farmacologia , Potentilla/química , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Animais , Antígenos CD , Antineoplásicos Fitogênicos/uso terapêutico , Caderinas/metabolismo , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Fibronectinas/metabolismo , Humanos , Neoplasias Pulmonares/patologia , Metaloproteinase 2 da Matriz/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Transplante de Neoplasias , Extratos Vegetais/uso terapêutico , Ativador de Plasminogênio Tipo Uroquinase/metabolismoRESUMO
A hydroxy-directed alkylation of an N,N-diethylarylamide using CIPE-assisted α-silyl carbanions (CIPE = complex-induced proximity effect) has been developed using a simple reagent combination of LDA (lithium diisopropylamide) and chlorosilane. A study of the mechanism, and the application of the procedure to an anionic Snieckus-Fries rearrangement for a highly efficient synthesis of the potent phosphatidylinositol 3-kinase (PI3K) inhibitorâ LY294002, are reported.
RESUMO
Cancer metastasis is the major cause of the high mortality risk of patients with osteosarcoma. Cinnamaldehyde has been shown to exhibit multiple tumour-suppressing activities, but its role in human osteosarcoma is not yet completely defined. In this study, the antimetastatic effect of cinnamaldehyde on highly metastatic human osteosarcoma cells was observed in vitro and in vivo using Saos-2 and 143B cells. Cinnamaldehyde reduced the activity and protein level of urokinase-type plasminogen activator (u-PA) and suppressed the invasion ability of osteosarcoma cells by inhibiting the phosphorylation of focal adhesion kinase. In addition, cinnamaldehyde reduced cell movement, cell-matrix adhesion, and the expression of the mesenchymal markers of epithelial-to-mesenchymal transition, namely, fibronectin and N-cadherin. Importantly, the oral administration of cinnamaldehyde remarkably suppressed the pulmonary metastasis of osteosarcoma in mice. Results indicated that cinnamaldehyde has therapeutic potential for inhibiting osteosarcoma metastasis.
Assuntos
Neoplasias Ósseas , Osteossarcoma , Transdução de Sinais , Acroleína/análogos & derivados , Animais , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Humanos , Camundongos , Osteossarcoma/tratamento farmacológico , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Ativador de Plasminogênio Tipo Uroquinase/metabolismoRESUMO
BACKGROUND: Understanding the relapse risk among different illicit drugs is vital for developing an adequate relapse prevention policy. Therefore, the current study aims to explore the potential difference in long-term relapse rates between youths who use ketamine and those who use stimulants (3,4-Methylenedioxymethamphetamine [MDMA] or methamphetamine). METHODS: The study's participants included 92 youths with ketamine use (ketamine group, mean age: 16.0 years) and 43 youths with MDMA/methamphetamine use (stimulants group, mean age: 16.1 years) that had undergone a family-oriented treatment program in a medical center in Taiwan. All participants were followed up for a maximum of 7 years in order to observe their long-term outcomes with regard to substance use relapse. RESULTS: During the follow-up period, compared to the 34.8% relapse rate in ketamine users, their counterparts who used MDMA or methamphetamine had a significantly higher relapse rate (60.5%, Adjusted HR = 1.86, 95%CI: 1.06-3.28, p = 0.032). Of the youths in the ketamine group that relapsed, 65.6% continued to use ketamine in their relapse event, while 34.4% switched to MDMA or methamphetamine. Among the relapsing youths in the stimulants group, 84.6% continued to use MDMA or methamphetamine in their relapse event, while 15.4% switched to ketamine (p = 0.042). CONCLUSIONS: Compared to adolescents who use ketamine, those using MDMA or methamphetamine had higher relapse rates and were more likely to use the same type of drug upon relapsing. These results can serve as a crucial reference for developing relapse prevention policies of illicit drugs for the youth population.
Assuntos
Ketamina/efeitos adversos , Metanfetamina/efeitos adversos , N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Estimulantes do Sistema Nervoso Central/efeitos adversos , Criança , Antagonistas de Aminoácidos Excitatórios/efeitos adversos , Feminino , Humanos , Masculino , Recidiva , Fatores de Risco , Taiwan/epidemiologiaRESUMO
BACKGROUND: To analyze the efficacy and safety of perampanel over a 3-month period in a sample of Asian people with epilepsy. METHODS: The efficacy and safety of perampanel as an adjunctive therapy for patients with epilepsy were retrospectively reviewed and analyzed. Patients were categorized according to seizure type, concomitant antiepileptic drug usage, and perampanel dosage. RESULTS: A total of 210 patients were included in the study and 131 patients completed 3 months of perampanel treatment. The average dosage of perampanel was 5.31 mg/day, and the 50% responder rate (≥50% seizure frequency reduction) in all patients was 45.8%, with a 27.5% seizure-free rate. For focal seizures, focal to bilateral tonic-clonic seizures, and primary generalized seizures, the 50% responder rates were respectively 29.4%, 49.5%, and 36.4%. In total, 39.5% of patients experienced adverse events within 3 months of observation period, and the rate of drug withdrawal due to adverse events was 8.6%. Dizziness, ataxia, irritability/aggression were the most common adverse events. CONCLUSIONS: The efficacy and safety of perampanel in a real-world setting with Asian patients is comparable to that in clinical trials that have included fewer Asian patients.
Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Piridonas/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas , Piridonas/efeitos adversos , Estudos RetrospectivosRESUMO
Many natural flavonoids have cytostatic and apoptotic properties; however, we little know whether the effect of synthetic 3-hydroxyflavone on metastasis and tumor growth of human osteosarcoma. Here, we tested the hypothesis that 3-hydroxyflavone suppresses human osteosarcoma cells metastasis and tumor growth. 3-hydroxyflavone, up to 50 µM without cytotoxicity, inhibited U2OS and 143B cells motility, invasiveness and migration by reducing matrix metalloproteinase (MMP)-2 and urokinase-type plasminogen activator (u-PA) and also impaired cell adhesion to gelatin. 3-hydroxyflavone significantly reduced p-focal adhesion kinase (FAK) Tyr397, p-FAK Tyr925, p-steroid receptor coactivator (Src), p-mitogen/extracellular signal-regulated kinase (MEK)1/2, p-myosin light chain (MLC)2 Ser19, epithelial cell adhesion molecule, Ras homolog gene family (Rho)A and fibronectin expressions. 3-hydroxyflavone also affected the epithelial-mesenchymal transition (EMT) by down-regulating expressions of Vimentin and α-catenin with activation of the transcription factor Slug. In nude mice xenograft model and tail vein injection model showed that 3-hydroxyflavone reduced 143B tumor growth and lung metastasis. 3-hydroxyflavone possesses the anti-metastatic activity of U2OS and 143B cells by affecting EMT and repressing u-PA/MMP-2 via FAK-Src to MEK/ERK and RhoA/MLC2 pathways and suppresses 143B tumor growth in vivo. This may lead to clinical trials of osteosarcoma chemotherapy to confirm the promising result in the future.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/prevenção & controle , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Flavonoides/farmacologia , Osteossarcoma/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Adolescente , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Miosinas Cardíacas/metabolismo , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Criança , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Humanos , Técnicas Imunoenzimáticas , MAP Quinase Quinase 1/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Cadeias Leves de Miosina/metabolismo , Osteossarcoma/metabolismo , Osteossarcoma/secundário , Células Tumorais Cultivadas , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína rhoA de Ligação ao GTP/metabolismo , Quinases da Família src/metabolismoRESUMO
Atherosclerosis is a chronic inflammatory vascular disease. It is characterized by endothelial dysfunction, lipid accumulation, leukocyte activation, and the production of inflammatory mediators and reactive oxygen species (ROS). Capsaicin, a biologically active compound of the red pepper and chili pepper, has several anti-oxidant, anti-inflammatory, anti-cancer, and hypolipidemic biological effects. However, its protective effects on foam cell formation and endothelial injury induced by oxidized low-density lipoprotein (oxLDL) remain unclear. In this study, we evaluated the anti-oxidative activity of capsaicin, and determined the mechanism by which capsaicin rescues human umbilical vein endothelial cells (HUVECs) from oxLDL-mediated dysfunction. The anti-oxidative activity of capsaicin was defined by Apo B fragmentation and conjugated diene production of the copper-mediated oxidation of LDL. Capsaicin repressed ROS generation, as well as subsequent mitochondrial membrane potential collapse, cytochrome c expression, chromosome condensation, and caspase-3 activation induced by oxLDL in HUVECs. Capsaicin also protected foam cell formation in macrophage RAW 264.7 cells. Our results suggest that capsaicin may prevent oxLDL-induced cellular dysfunction and protect RAW 264.7 cells from LDL oxidation.
Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Capsaicina/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Lipoproteínas LDL/antagonistas & inibidores , Lipoproteínas LDL/química , Macrófagos/efeitos dos fármacos , Capsaicina/química , Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Lipoproteínas LDL/farmacologia , Macrófagos/metabolismo , Oxirredução/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
Koelreuteria formosana ethanol extract (KFEE) is obtained from natural plants that are endemic in Taiwan. A study showed that KFEE has antioxidant activity in DPPH assay. In the current study, the antioxidative activity of KFEE, which contains polyphenols including gallic acid and caffeic acid, was evaluated. The manner by which KFEE protects human umbilical vein endothelial cells (HUVECs) from oxidised LDL (oxLDL)-mediated dysfunction in vitro was investigated as well. The results indicate that the antioxidative activity of KFEE is defined by the relative electrophoretic mobility of oxLDL, the fragmentation of ApoB, conjugated diene production, and malondialdehyde production through Cu(2+)-mediated oxidation of LDL. KFEE also inhibited ROS generation as well as the subsequent mitochondrial membrane potential collapse, chromosome condensation, cytochrome C release, and caspase-3 activation induced by oxLDL in HUVECs. Our results also indicate that KFEE may protect LDL oxidation and prevent oxLDL-induced cellular dysfunction in HUVECs.
Assuntos
Apoptose/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Lipoproteínas LDL/metabolismo , Extratos Vegetais/farmacologia , Sapindaceae/química , Caspase 3/metabolismo , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/enzimologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Oxirredução , Extratos Vegetais/isolamento & purificação , Espécies Reativas de Oxigênio/metabolismoRESUMO
Koelreuteria formosana ethanolic extract (KFEE) is obtained from natural plants that are endemic to Taiwan. In a previous study, it was demonstrated that KFEE inhibited low-density lipoprotein (LDL) and prevented oxidized LDLinduced apoptosis in endothelial cells. In the present study, KFEE was shown to inhibit the invasion and migration of 786OSI3 renal cell carcinoma (RCC) cells while not exhibiting any cytotoxic effects. 786OSI3 cells were treated with KFEE at numerous concentrations of ≤100 µg/ml for 24 h. In order to examine the effects of KFEE, cells were then subjected to a series of assays for cell viability (MTT), wound healing migration, cell invasion and migration, gelatin zymography, casein zymography and immunofluorescence, as well as western blot analysis. KFEE was shown to decrease levels of matrix metalloproteinase2, phosphorylated (p)focal adhesion kinase Try925, ppaxillin Ser178, pmitogenactivated protein kinase kinase 1/2, pmyosin light chain and pextracellular signal-regulated kinase 1/2 in 786-0-SI3 cells. Reduction of lung metastases was observed in KFEE-treated mice compared with vehicletreated control mice. KFEE inhibited the invasion of RCC cells and may have the potential for use as a chemopreventive agent against RCC metastasis.
Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Renais/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Neoplasias Renais/tratamento farmacológico , Invasividade Neoplásica/prevenção & controle , Extratos Vegetais/farmacologia , Animais , Carcinoma de Células Renais/genética , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Proteína-Tirosina Quinases de Adesão Focal/genética , Humanos , Neoplasias Renais/genética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Masculino , Metaloproteinase 2 da Matriz/genética , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/genética , Cadeias Leves de Miosina/genética , Invasividade Neoplásica/genética , Paxilina/genéticaRESUMO
Epithelial-to-mesenchymal transition (EMT) in cancer cells is considered to be a prerequisite for acquiring invasive/migratory phenotype and subsequent metastasis. This study provides molecular evidence associated with the antimetastatic effect of black tea polyphenol extracts (BTE), which contain polyphenols including gallic acid, gallocatechin, catechin, epigallocatechin-3-gallate, epicatechin-3-gallate, and theaflavin 3,3'-digallate, in an an oral squamous cell culture system by showing a nearly complete inhibition on the invasion (p < 0.001) of SCC-4 cells via reduced activities of MMP-2 (p < 0.001) and u-PA (p < 0.001). Immunoblot was performed to find that BTE could induce up-regulation of epithelial markers such as E-cadherin and inhibit mesenchymal markers such as snail-1 and vimentin. BTE inhibited p-FAK and p-paxillin, indicating the anti-EMT effect of BTE in oral squamous cell carcinoma. BTE was evidenced by its inhibition of the tumor growth of SCC-4 cells via cancer cell xenografted nude mice mode. These results suggested that BTE could reduce invasion by reversing EMT in human oral cancer cells.