RESUMO
Ethanol extracts of Cnidii Fructus, the dried fruits of Cnidium monnieri (L.) Cusson, have been externally applied in the treatment of Trichomonas vaginalis. However, the precise identity of the major constituents responsible for activity against T. vaginalis is unknown, but there is probability they are coumarin derivatives. In this study, the anti-Trichomonas activity of 4 major coumarin derivative constituents of Cnidii Fructus, namely, osthole, xanthotoxin, isopimpinellin, and bergapten, was characterized in terms of the resulting kinetics of growth and morphology of T. vaginalis upon treatment. The results demonstrated that osthole and xanthotoxol had significant trichomonacidal ability, while isopimpinellin and bergapten displayed low or no inhibitory efficacy toward T. vaginalis parasites. Our study suggests that the coumarin derivatives osthole and xanthotoxol can be potentially used as a basis for the development and design of new drugs for application in alternative or synergistic therapy against T. vaginalis.
RESUMO
BACKGROUND/AIM: Matrix metalloproteinase-2 (MMP-2) plays a critical role in the regulation of the extracellular matrix; however, its genotypes have seldom been examined in gastric cancer (GC). This study aimed to investigate the contribution of MMP-2 promoter -1306 (rs243865) and -735 (rs2285053) genotypes to GC risk in a cohort of Taiwanese individuals. MATERIALS AND METHODS: This study included 121 GC cases and 363 age- and sex-matched controls. The genotypes of MMP-2 were determined by typical polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The genotypic and allelic frequency analysis showed that MMP-2 rs243865 variant genotypes decreased the risk of GC. Stratification analysis showed that MMP-2 rs243865 genotypes associate with smoking, alcohol drinking, and Helicobacter pylori infection status to confer personal susceptibility to GC. There is no such association for MMP-2 rs2285053 genotype with GC risk. CONCLUSION: The MMP-2 rs243865 genotypes may serve as a novel predictive marker for GC personal susceptibility among Taiwanese.
Assuntos
Metaloproteinase 2 da Matriz , Neoplasias Gástricas , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Infecções por Helicobacter/complicações , Humanos , Metaloproteinase 2 da Matriz/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética , Taiwan/epidemiologiaRESUMO
BACKGROUND/AIM: Breast cancer incidence is highest among women worldwide, and practical markers for personalized therapeutic strategies are few. Interleukin-12 (IL-12) is a cytokine that is reported to be significantly lower in healthy controls than breast cancer cases, however, its genotypic contribution to carcinogenesis has never been revealed in breast cancer. We examined whether IL-12A rs568408 and rs2243115 genotypes contribute to elevated breast cancer risk and summarized related literature among other cancers. MATERIALS AND METHODS: IL-12A genotypic profiles were determined among 1,232 breast cancer cases and 1,232 healthy controls via polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The variant genotypes of IL-12A rs568408 and rs2243115 were not found to be significantly associated with elevated breast cancer risk (both p>0.05). CONCLUSION: IL-12A rs568408 and rs2243115 genotypes may not serve as good predictors of breast cancer risk.
Assuntos
Neoplasias da Mama/genética , Estudos de Associação Genética/métodos , Subunidade p35 da Interleucina-12/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Polimorfismo de Fragmento de RestriçãoRESUMO
BACKGROUND/AIM: Matrix metalloproteinase 9 (MMP9) is highly expressed in gastric cancer but the role of MMP9 is unclear. This study aimed at revealing the association of MMP9 promoter rs3918242 genotypes with gastric cancer risk. MATERIALS AND METHODS: MMP9 rs3918242 genotypes of 121 patients with gastric cancer and 363 healthy individuals were examined by polymerase chain reaction-restriction fragment length polymorphism methodology using serum samples. RESULTS: MMP9 rs3918242 TT genotype carriers had an elevated gastric cancer risk compared to wild-type CC carriers (odds ratio=3.92, 95% confidence interval=1.28-11.99; p=0.0103). Patients with CT/TT genotypes were at higher risk of metastasis (p=0.0178) than those with CC. No correlation was found between MMP9 rs3918242 genotype and gastric cancer risk with smoking or alcohol behavior, nor Helicobacter pylori infection. No correlation was observed for MMP9 rs3918242 genotypic distributions with age, gender, or body mass index. CONCLUSION: Carrying a T allele for MMP9 rs3918242 may be predictive for higher gastric cancer risk, and as a predictor for higher risk of metastasis.
Assuntos
Predisposição Genética para Doença/genética , Metaloproteinase 9 da Matriz/genética , Regiões Promotoras Genéticas/genética , Neoplasias Gástricas/genética , Estudos de Casos e Controles , Feminino , Genótipo , Infecções por Helicobacter/genética , Helicobacter pylori/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição/genética , Fatores de RiscoRESUMO
BACKGROUND/AIM: The molecular mechanisms underlying the association between cell cycle and asthma are poorly understood, and cyclin D1 (CCND1) is found to be upregulated in asthma airway smooth muscle. We investigated whether the most frequently examined functional variants in CCND1 determine asthma susceptibility. MATERIALS AND METHODS: We genotyped 651 participants for single-nucleotide polymorphisms (SNPs) at rs9344 and rs678653 on CCND1 and assessed the association of these SNPs with asthma risk. RESULTS: Significant differences were found in the distributions of genotypic (p=0.0064) and allelic (p=0.0021) frequencies of CCND1 rs9344. In addition, AG or GG carriers had 0.63- or 0.48-fold adjusted odds ratios for asthma risk (95%confidence intervals=0.48-0.92 and 0.22-0.78, respectively) than those who carried the AA wildtype. CONCLUSION: Our results suggest that cell cycle regulation may play a role in asthma initiation and development, and the CCND1 rs9344 genotype may serve as an early detection marker for asthma.
Assuntos
Asma , Ciclina D1 , Asma/genética , Estudos de Casos e Controles , Ciclina D1/genética , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Taiwan/epidemiologiaRESUMO
BACKGROUND/AIM: Xeroderma pigmentosum complementation group C (XPC) is reported to play important roles in DNA integrity and genomic instability, however, the contribution of XPC to oral carcinogenesis is largely uncertain. Therefore, we aimed at examining the contribution of XPC genotypes to oral cancer. MATERIALS AND METHODS: The genotypes of XPC rs2228001 and rs2228000 were examined among 958 oral cancer patients and 958 control subjects by polymerase chain reaction-restriction fragment length polymorphism methodology and corresponding DNA repair capacity was checked. RESULTS: First, the percentages of XPC rs2228001 AC and CC were higher among oral cancer patients than controls. Second, no significant association was observed regarding XPC rs2228000. Third, there was a synergistic influence of smoking and betel quid chewing behaviors and XPC rs2228001 genotype on oral cancer risk. Last, functional experiments showed DNA repair capacity was lower for AC/CC carriers than AA carriers. CONCLUSION: XPC rs2228001 C allele, which was associated with decreased DNA repair capacity, may interact with smoking and betel quid chewing behaviors on oral cancer risk.
Assuntos
Areca/química , Reparo do DNA/genética , Proteínas de Ligação a DNA/metabolismo , Neoplasias Bucais/etiologia , Neoplasias Bucais/genética , Fumar/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologiaRESUMO
BACKGROUND/AIM: Matrix metalloproteinase-1 is responsible for extracellular matrix regulation, and its genetic role in colorectal cancer (CRC) is unclear. The aim of the study was to investigate the contribution of Matrix metalloproteinase-1 genotypes to CRC risk in Taiwan. MATERIALS AND METHODS: A total of 362 cases and 362 controls were included and their MMP-1 -1607 (rs1799705) genotypes were examined. The environmental factors and clinical-pathological records were also analyzed. RESULTS: The genotypic frequency of MMP-1 rs1799750 were different between the CRC and control groups (p for trend=0.0083). 1G/2G and 1G/1G were associated with lower risk (p=0.0438 and 0.0030, adjusted OR=0.73 and 0.54, 95%CI=0.54-0.90 and 0.37-0.83). Among non-smokers, those with 1G/2G and 1G/1G genotypes were at 0.70- and 0.48-fold odds of having CRC. Among non-alcohol drinkers, people with 1G/2G and 1G/1G genotypes were at 0.71- and 0.54-fold odds. The 1G/1G genotype were statistically lower among CRC patients with lymph node metastasis (7.2%) than those without (19.0%). CONCLUSION: The genotypes at MMP-1 rs1799705 play a role in determining susceptibility to CRC risk in Taiwan.
Assuntos
Neoplasias Colorretais/genética , Metaloproteinase 1 da Matriz/genética , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Taiwan/epidemiologiaRESUMO
BACKGROUND/AIM: Interleukin-16 (IL-16) is reported to play an important role in inflammation, carcinogenesis and tumoricidal processes, however, the contribution of IL-16 genotype to oral carcinogenesis is still largely unrevealed. Thus, the study aimed to investigate the contribution of IL-16 genotypes to Taiwan oral cancer risk. MATERIALS AND METHODS: The genotypes of IL-16 rs4778889, rs11556218, and rs4072111 were revealed among 958 oral cancer cases and 958 control subjects by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). RESULTS: First, the distributions of genotypic (p=0.0004) and allelic (p=0.0001) frequencies of IL-16 rs11556218 were significantly different between the case and control groups. In detail, the frequencies of IL-16 rs11556218 TG and GG were 28.1 and 5.8%, respectively, among oral cancer patients, significantly higher compared to those among controls (25.0% and 2.7%, respectively). Second, no difference was observed regarding IL-16 rs4778889 or IL-16 rs4072111. Last, there was a synergistic effect of betel quid chewing behavior and risky IL-16 rs11556218 genotype on oral cancer risk. CONCLUSION: The study indicates that the IL-16 rs11556218 G allele synergistically interacts with betel quid chewing behavior, contributing to increased risk of oral cancer in Taiwanese.
Assuntos
Interleucina-16 , Neoplasias Bucais , Areca/efeitos adversos , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Humanos , Interleucina-16/genética , Mastigação , Neoplasias Bucais/etiologia , Neoplasias Bucais/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Taiwan/epidemiologiaRESUMO
BACKGROUND/AIM: The present study aimed at evaluating the contribution of IL-4 promoter T-1099G (rs2243248), C-589T (rs2243250), C-33T (rs2070874) genotypes to the risk of breast cancer in Taiwanese. MATERIALS AND METHODS: A total of 1232 breast cancer patients and 1232 age-matched controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS: Genotypic frequencies of IL-4 rs2243248, rs2243250 and rs2070874 were not differentially distributed between case and control groups. Consistently, there was no difference in the distribution of allelic frequencies among patients and controls. CONCLUSION: IL-4 rs2243248, rs2243250 and rs2070874 do not confer breast cancer susceptibility in Taiwanese.
Assuntos
Neoplasias da Mama/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Interleucina-4/genética , Polimorfismo de Nucleotídeo Único , Idoso , Idoso de 80 Anos ou mais , Alelos , Povo Asiático/genética , Neoplasias da Mama/epidemiologia , Feminino , Frequência do Gene , Genótipo , Humanos , Pessoa de Meia-Idade , Razão de Chances , Regiões Promotoras Genéticas , Medição de Risco , TaiwanRESUMO
Oxidative stress may play critically important roles in the etiology of Parkinson's disease (PD). 6-Hydroxydopamine (6-OHDA) is a physiological neurotoxin reported to induce oxidative-induced apoptosis of dopaminergic neurons in PD mice models. Valproic acid (VPA), a clinical mood stabilizer, is a HDAC inhibitor with neuroprotective capacities. In the study, we aim at examining the feasibility of VPA as a protector for dopaminergic neurons against damage from 6-OHDA, and the intracellular mechanisms. The 6-OHDA-induced neurotoxicity to the human dopaminergic cell line SH-SY5Y was applied for examining VPA protective effects. Pretreatment with VPA was able to improve cell viability and reduce 6-OHDA-induced reactive oxygen species. Furthermore, a significant suppression of apoptotic caspases including cleaved caspase-3, caspase-7, and caspase-9 was observed. The results also revealed VPA decreased the 6-OHDA-induced Bax/Bcl2 ratio, as measured at protein level. These novel findings indicate that VPA may be capable of protecting the SH-SY5Y dopaminergic neuronal cells from 6-OHDA-induced toxicity via the deceasing of apoptotic caspases (cleaved caspase-3, caspase-7, and caspase-9) and reducing of the Bax/Bcl2 ratio. Very possibly, VPA could serve as not only a mood stabilizer but also a potential antidote for PD prevention.
Assuntos
Fármacos Neuroprotetores/farmacologia , Oxidopamina/toxicidade , Ácido Valproico/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3 , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dopamina/metabolismo , Humanos , Camundongos , Neurônios/efeitos dos fármacos , Síndromes Neurotóxicas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Oxidopamina/metabolismo , Oxidopamina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Ácido Valproico/metabolismoRESUMO
AIM: To investigate the association between adiponectin (ADIPOQ) genotypes and colorectal cancer (CRC) risk among Taiwanese. MATERIALS AND METHODS: Polymerase chain reaction-restriction fragment length polymorphism was adopted to identify ADIPOQ rs266729, rs2241766 and rs1501299 genotypes among 362 CRC patients and 362 healthy controls. RESULTS: ADIPOQ rs266729 GG genotype (p=0.0075) and G allele (p=0.0061) are associated with a significantly increased CRC risk. There is no differential distribution of rs2241766 and rs1501299 genotypes. As for the gene-lifestyle interaction, there are obvious joint effects of rs266729 genotype on the CRC risk among non-smoker, non-alcohol drinker, while not on smoker or non-drinker subgroups. No significant correlation was observed between rs266729 genotypic distributions and age, gender, tumor size, location or metastasis status. Interestingly, a correlation of rs266729 genotype and larger BMI on CRC risk was found. CONCLUSION: G allele at ADIPOQ rs266729 may serve as a determiner for CRC risk, especially for those with BMI ≥24.
Assuntos
Adiponectina/metabolismo , Neoplasias Colorretais/genética , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , TaiwanRESUMO
The DNA repair capacity plays a critical role in maintaining the genomic stability and gatekeeping for individual cancer risk. In this study, we aim at evaluation the role of the Asp148Glu (rs1130409) variant at apurinic/apyrimidinic endonuclease (APE) gene in renal cell carcinoma (RCC) risk and the contribution of different genotypes to its transcriptional mRNA levels. In the case-control study, 92 RCC patients and 580 cancer-free patients matched by age and gender were recruited. The apurinic/APE genotyping work was conducted with typical restriction fragment length polymorphism methodology after polymerase chain reaction. At the meanwhile, thirty renal tissue samples with variant genotypes were examined for their apurinic/APE mRNA and protein expressions by real-time quantitative reverse transcription method and Western blotting. The results showed that compared with the wild-type TT genotype, the people with TG and GG genotypes of apurinic/APE Asp148Glu had 0.88- and 1.09-fold risk of RCC, respectively. We have also examined the in vivo transcriptional (RNA) and translational (protein) levels with renal tissues of various apurinic/APE Asp148Glu genotypes, revealing that the apurinic/APE mRNA and protein were of similar levels among people of TT, TG, or GG genotypes. There was no joint gene-environment effect of apurinic/APE Asp148Glu genotype and smoking habit on RCC risk. The evidence indicated that apurinic/APE Asp148Glu genotypic variants did not alter its mRNA and protein expression among RCC patients. The genotype of apurinic/APE Asp148Glu may not serve as a proper predictive marker for RCC risk in Taiwan.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Estudos de Casos e Controles , Reparo do DNA , DNA Liase (Sítios Apurínicos ou Apirimidínicos) , Endonucleases , Genótipo , Humanos , Fenótipo , TaiwanRESUMO
BACKGROUND/AIM: Few studies have examined the genetic role of matrix metalloproteinases (MMPs) to early detection or prediction in gastric cancer development. In this study, the contribution of MMP7 promoter (A-181G and C-153T) polymorphic genotypes to gastric cancer risk in Taiwanese was investigated for the first time. MATERIALS AND METHODS: A total of 121 cases and 363 controls were enrolled and their MMP7 genotypes at A-181G and C-153T were examined by polymerase chain reaction-restriction fragment length polymorphism methodology using genomic DNA from serum. RESULTS: The GG genotype at MMP7 A-181G was found to represent a risk factor for gastric cancer, especially among smokers. No individual with variant genotype carrier at MMP7 C-153T was found among this Taiwanese population. CONCLUSION: The G allele of MMP7 A-181G may serve as an early predictor for gastric cancer risk in Taiwanese; other gastric cancer markers are still urgently needed.
Assuntos
Metaloproteinase 7 da Matriz/genética , Neoplasias Gástricas/genética , Povo Asiático/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de Risco , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/patologia , TaiwanRESUMO
BACKGROUND/AIM: Few studies have examined the contribution of matrix metalloproteinases (MMP) to either diagnosis or prognosis of pterygium. The aim of this study was to investigate the contribution of MMP-1 genotypes to pterygium risk. PATIENTS AND METHODS: A total of 134 cases and 268 controls were included and their MMP-1 -1607 (rs1799705) genotypes were examined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The percentages of 2G/2G, 1G/2G, and 1G/1G for rs1799705 genotypes were 48.5, 36.6 and 14.9% among patients and 33.9, 44.8, and 21.3% among controls (p trend=0.0167). The odds ratios (ORs) after adjusting for age and gender for 1G/2G and 1G/1G genotypes at rs1799705 were 0.54 (95%CI=0.33-0.89, p=0.0168) and 0.46 (95%CI=0.27-0.88, p=0.0192), respectively. Consistently, the adjusted OR for those carrying the 1G allele at MMP-1 -1607 was 0.61 (95%CI=0.41-0.78, p=0.0167), compared with the wild-type 2G allele. CONCLUSION: The genotypes at rs1799705 play a role in determining personal susceptibility to pterygium.
Assuntos
Metaloproteinase 1 da Matriz/genética , Pterígio/genética , Idoso , Idoso de 80 Anos ou mais , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Pterígio/enzimologia , Pterígio/epidemiologia , Taiwan/epidemiologiaRESUMO
BACKGROUND/AIM: In literature, few studies have examined the diagnostic or prognostic potential of matrix metalloproteinases (MMP) in pterygium, whose formation and progression are closely related to imbalance in the extracellular microenvironment. In this study, we investigated the contribution of MMP7 promoter (A-181G and C-153T) polymorphic genotypes to pterygium risk. MATERIALS AND METHODS: A total of 134 cases and 268 controls were collected and their MMP7 genotypes at A-181G and C-153T were examined by polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The AA, AG and GG genotypes at MMP7 promoter A-181G were non-significantly differentially distributed between the two groups at 85.8, 11.2 and 3.0%, respectively, in pterygium cases and 88.4, 9.7 and 1.9% in controls, respectively (p for trend=0.6822). There was no polymorphic genotype for MMP7 C-153T among our Taiwanese cohort. CONCLUSION: A-181G and C-153T genotypes at MMP7 do not have a direct role in determining Taiwanese susceptibility to pterygium.
Assuntos
Predisposição Genética para Doença/genética , Metaloproteinase 7 da Matriz/genética , Pterígio/genética , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição/genética , Polimorfismo de Nucleotídeo Único/genética , Prognóstico , Regiões Promotoras Genéticas/genética , Fatores de RiscoRESUMO
BACKGROUND/AIM: Oral cancer is of the highest incidence worldwide in Taiwan, and a better marker for personalized therapeutic strategies such as immunotherapies is urgently needed. Interleukin-12 (IL12) is a cytokine that has been reported to exhibit potent tumoricidal effects, however, its genotypic contribution to oral cancer is still largely unknown. The current study aimed at investigating whether IL12B rs3212227 genotype is associated with oral cancer in Taiwan. MATERIALS AND METHODS: Genotypic characteristics of IL12B rs3212227 were determined among 958 oral cancer cases and age- and gender-matched individuals via typical polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS: The AA, AC and CC genotypes of IL12B rs3212227 were 38.2, 38.9 and 22.9% in the case group and 36.2, 41.5 and 22.3% in the control group (p=0.5189), respectively. CONCLUSION: IL12B rs3212227 genotype was associated with oral cancer risk only in betel quid chewers.
Assuntos
Areca/efeitos adversos , Subunidade p40 da Interleucina-12/genética , Neoplasias Bucais/genética , Polimorfismo de Nucleotídeo Único , Idoso , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Testes Genéticos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/induzido quimicamente , TaiwanRESUMO
Interleukin-18 (IL-18) is a multi-functional immuno-mediator in the development and progression of many types of infectious and inflammatory diseases. In this study, we evaluated the contribution of IL-18 genotypes to renal cell carcinoma (RCC) in Taiwan via the genotyping of IL-18 -656 (A/C), -607 (A/C), and -137 (G/C). Moreover, we analyzed their interactions with smoking, alcohol drinking, hypertension, and diabetes status. The results showed an association of the AC and CC genotypes of IL-18 -607 with a significant decrease in the risk of RCC compared with the AA genotype (odds ratio (OR) = 0.44 and 0.35, 95% confidence interval (CI) = 0.27â»0.72 and 0.18â»0.66, p = 0.0008 and 0.0010, respectively). Furthermore, a significantly lower frequency of the C allele at -607 was observed in the RCC group (35.3% vs. 49.8%; OR = 0.53; 95% CI = 0.35â»0.71, p = 0.0003). However, IL-18 -656 and -137 did not exhibit a likewise differential distribution of these genotypes between the control and case groups. Stratifying the population according to smoking, alcohol drinking, hypertension, and diabetes status revealed a different distribution of IL-18 -607 genotypes among non-smokers, non-drinkers, and patients without diabetes, but not among smokers, drinkers, or patients with diabetes. These findings suggest that IL-18 -607 genotypes may play a role in the etiology and progression of RCC in Taiwan and may serve as a useful biomarker for early detection.
Assuntos
Carcinoma de Células Renais/genética , Interleucina-18/genética , Neoplasias Renais/genética , Polimorfismo de Nucleotídeo Único , Idoso , Carcinoma de Células Renais/epidemiologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Neoplasias Renais/epidemiologia , Masculino , Pessoa de Meia-Idade , Taiwan/epidemiologiaRESUMO
Cantharidin (CTD), a component of natural mylabris (Mylabris phalerata Pallas), has been shown to have biological activities and induce cell death in many human cancer cells. In the present study, we investigated the effect of CTD on cell migration and invasion of NCI-H460 human lung cancer cells. Cell viability was examined and results indicated that CTD decreased the percentage of viable cells in dose-dependent manners. CTD inhibited cell migration and invasion in dose-dependent manners. Gelatin zymography analysis was used to measure the activities of matrix metalloproteinases (MMP-2/-9) and the results indicated that CTD inhibited the enzymatic activities of MMP-2/-9 of NCI-H460 cells. Western blotting was used to examine the protein expression of NCI-H460 cells after incubation with CTD and the results showed that CTD decreased the expression of MMP-2/-9, focal adhesion kinase (FAK), Ras homolog gene family, member A (Rho A), phospho-protein kinase B (AKT) (Thr308)(p-AKT(308)), phospho-extracellular signal-regulated kinase1/2 (p-ERK1/2), phospho-p38 mitogen-activated protein (MAP) kinase (p-p38), phospho c-Jun N-terminal kinase 1/2 (p-JNK1/2), nuclear factor-κB (NF-κB) and urokinase plasminogen activator (UPA). Furthermore, confocal laser microscopy was used to confirm that CTD suppressed the expression of NF-κB p65, but did not significantly affect protein kinase C (PKC) translocation in NCI-H460 cells. Based on those observations, we suggest that CTD may be used as a novel anticancer metastasis agent for lung cancer in the future.
Assuntos
Cantaridina/farmacologia , Movimento Celular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Neoplasias Pulmonares/patologia , Sistema de Sinalização das MAP Quinases , Invasividade Neoplásica/prevenção & controle , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/enzimologiaRESUMO
4-Hydroxybutenolide (K87), a synthetic compound from furfuryl alcohol via photooxidation, was used to investigate whether it can inhibit mobility, migration and invasion of SCC-4 human oral cancer cells in vitro. Cell viability was measured by flow cytometric assay, the enzymatic activities of MMP-2/9 were assayed by gelatin zymography analysis, the protein levels were assayed by western blotting, confocal laser microscopy and EMSA assay, and the gene expression of MMP-2/-7, FAK and ROCK1 mRNA were assayed by PCR. K87 decreased the percentage of viable cells in dose-dependent manner. K87 suppressed cell mobility, migration and invasion of SCC-4 cells dose-dependently. K87 inhibited the enzymatic activities of MMP-2/9 of SCC-4 cells. Western blot analysis revealed that K87 decreased the protein levels in NF-κBp65, COX-2, ROCK1 and Rho A, MMP-1, -2,- 7, -9, VEGF, GRB2, SOS1, PI3K, PKC, PERK, p-PERK, FAK, MEKK3, MKK7, ERK1/2, JNK1/2, p-p38, p38, p-c-Jun, AKT, TIMP2, but increased the protein levels of iNOS, Ras, IRE-1α, p-c-JNK, p-AKT(308), p-AKT(473) and TIMP1. Results from PCR indicated that K87 inhibited the gene expression of MMP-2/-7, FAK and ROCK1 mRNA. Furthermore, confocal laser microscopy was used to confirm that K87 inhibited the translocation of RHOA and ROCK1 in SCC-4 cells. EMSA assay also show that K87 suppressed the nuclear activation of NF-κB and these effects are time-dependent. Western blotting assay indicated that expression of NF-κBp105, NF-κBp50 and NF-κBp65 proteins were decreased and these effects are time-dependent. Based on these observations, we suggest that K87 may be used as a potential agent for anticancer metastasis of human oral cancer in the future.
Assuntos
4-Butirolactona/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neoplasias Bucais/tratamento farmacológico , NF-kappa B/antagonistas & inibidores , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/farmacologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , NF-kappa B/metabolismo , Invasividade Neoplásica , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
Isothiocyanates (ITCs) occur in many cruciferous vegetables. These compounds, which have significant anticancer actions, can induce apoptosis in different human cancer cell lines. In the present study, we investigated if allyl isothiocyanate (AITC) would induce toxicity in human breast cancer MCF-7 (estrogen receptor positive) and MDA-MB-231 (estrogen receptor negative) cells. We found that AITC stimulated reactive oxygen species and Ca[Formula: see text] production, and decreased the mitochondrial membrane potential. Activity of caspase-8, -9 and -3 was increased by AITC in both cell lines. AITC also induced mitochondrial-mediated apoptosis, as shown by cytochrome c, AIF and Endo G release from mitochondria, activation of caspase-9 and caspase-3, and formation of DAPI-positive cells. There was a significant reduction in the levels of the anti-apoptotic protein Bcl-2 along with a marked increase in the pro-apoptotic protein Bax in both cell lines. AITC induced apoptosis in human breast cancer MCF-7 cells via AIF and Endo G signaling pathways, but in MDA-MB-231 cells apoptosis occurred via the GADD153 pathway. This study has revealed novel anti-cancer mechanisms of AITC, a compound that is ordinarily present in human diets and may have potential therapeutic effects in various cancers.