ABSTRACT
Coronary artery disease (CAD), a multifactorial disease, is a common cause of mortality in humans. Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene (-786T>C, 4a4b, and 894G>T) have been previously associated with increased CAD risk. However, the sample size of this previous study was too small and limited to comprehensively define an association between eNOS polymorphisms and CAD; therefore, this analysis was duplicated with a larger population. The study was conducted on 559 patients with CAD and 574 healthy controls. Genetic DNA was extracted using the commercial G-DEX blood extraction kit and statistical analyses were performed on the GraphPad prism 4.0 and MedCalc 12.0 statistical software platforms. No single variant of the eNOS polymorphism was associated with CAD risk. The combination genotypes of eNOS -786TT/4a4b+4a4a [adjusted odds ratio (AOR) = 0.122; 95% confidence interval (CI): 0.042-0.358] and eNOS -786TC+CC/4b4b (AOR = 0.379; 95%CI: 0.147-0.979) were associated with decreased CAD incidence. Haplotype analysis revealed that the T-4a haplotype of eNOS -786T>C and 4a4b exerted a protective effect against CAD. The association between eNOS -786T>C and increased CAD risk was not replicated in this (larger) population. However, some combined genotypes showed a meaningful association with CAD risk.
Subject(s)
Asian People/genetics , Coronary Artery Disease/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Nitric Oxide Synthase Type III/genetics , Polymorphism, Genetic , Aged , Alleles , Case-Control Studies , Comorbidity , Coronary Artery Disease/blood , Coronary Artery Disease/epidemiology , Female , Folic Acid/blood , Gene Frequency , Genotype , Haplotypes , Homocysteine/blood , Humans , Linkage Disequilibrium , Male , Middle Aged , Odds Ratio , Polymorphism, Single Nucleotide , Republic of Korea/epidemiology , Risk , Risk FactorsABSTRACT
Pancreatic cancer is the fourth leading cause of cancer death. Gemcitabine is widely used as a chemotherapeutic agent for the treatment of pancreatic cancer, but the prognosis is still poor. Berberine, an isoquinoline alkaloid extracted from a variety of natural herbs, possesses a variety of pharmacological properties including anticancer effects. In this study, we investigated the anticancer effects of berberine and compared its use with that of gemcitabine in the pancreatic cancer cell lines PANC-1 and MIA-PaCa2. Berberine inhibited cell growth in a dose-dependent manner by inducing cell cycle arrest and apoptosis. After berberine treatment, the G1 phase of PANC-1 cells increased by 10% compared to control cells, and the G1 phase of MIA-PaCa2 cells was increased by 2%. Whereas gemcitabine exerts antiproliferation effects through S-phase arrest, our results showed that berberine inhibited proliferation by inducing G1-phase arrest. Berberine-induced apoptosis of PANC-1 and MIA-PaCa2 cells increased by 7 and 2% compared to control cells, respectively. Notably, berberine had a greater apoptotic effect in PANC-1 cells than gemcitabine. Upon treatment of PANC-1 and MIA-PaCa2 with berberine at a half-maximal inhibitory concentration (IC50), apoptosis was induced by a mechanism that involved the production of reactive oxygen species (ROS) rather than caspase 3/7 activation. Our findings showed that berberine had anti-cancer effects and may be an effective drug for pancreatic cancer chemotherapy.
Subject(s)
Adult , Female , Humans , Middle Aged , Attention Deficit Disorder with Hyperactivity , Child Psychiatry/education , Faculty , Learning Disabilities , Professional Competence/standards , Analysis of Variance , Brazil , Feasibility Studies , Schools , Self Report , Social Adjustment , Surveys and QuestionnairesABSTRACT
Pancreatic cancer is the fourth leading cause of cancer death. Gemcitabine is widely used as a chemotherapeutic agent for the treatment of pancreatic cancer, but the prognosis is still poor. Berberine, an isoquinoline alkaloid extracted from a variety of natural herbs, possesses a variety of pharmacological properties including anticancer effects. In this study, we investigated the anticancer effects of berberine and compared its use with that of gemcitabine in the pancreatic cancer cell lines PANC-1 and MIA-PaCa2. Berberine inhibited cell growth in a dose-dependent manner by inducing cell cycle arrest and apoptosis. After berberine treatment, the G1 phase of PANC-1 cells increased by 10% compared to control cells, and the G1 phase of MIA-PaCa2 cells was increased by 2%. Whereas gemcitabine exerts antiproliferation effects through S-phase arrest, our results showed that berberine inhibited proliferation by inducing G1-phase arrest. Berberine-induced apoptosis of PANC-1 and MIA-PaCa2 cells increased by 7 and 2% compared to control cells, respectively. Notably, berberine had a greater apoptotic effect in PANC-1 cells than gemcitabine. Upon treatment of PANC-1 and MIA-PaCa2 with berberine at a half-maximal inhibitory concentration (IC50), apoptosis was induced by a mechanism that involved the production of reactive oxygen species (ROS) rather than caspase 3/7 activation. Our findings showed that berberine had anti-cancer effects and may be an effective drug for pancreatic cancer chemotherapy.