Small-molecule inhibitors targeted MAPK have been wildly used for some cancer therapeutics as a biologically viable model, but no one has been used for cervical caner. ERK1/2, one of MAPK kinases, is expressed high in cervical cancer tissue. The aim of the present study was to evaluate the effects of ERK1/2 inhibitor U0126 on proliferation and apoptosis of cervical cancer cells and appraise the correlated mechanism of the effects. In this study, the cell proliferation of Hela and C33A cervical cancer cells was tested by Cell Counting Kit-8 (CCK8) assay and cell counting after treated with ERK1/2 inhibitor U0126. The cell cycle and apoptosis were evaluated by flow cytometry (FCM). The protein levels of ERK1/2 and c-Fos and c-Jun were detected by Western blot. The results indicated that after down-regulating ERK1/2 proteins with the inhibitor U0126, Hela and C33A cells proliferation was inhibited, cell apoptosis was promoted, the proportions of G0/G1 stage in cell cycle increased, and G2/M stages decreased. After down-regulating ERK1/2 proteins of Hela and C33A cells, the expression levels of p-c-Fos protein decreased, while p-c-Jun protein increased. The results of this study indicated that ERK1/2 may promote the development of cervical cancer cells, suggesting ERK1/2 inhibitor may be used as an effective target for cervical cancer therapies working for. It might inhibit cervical cancer cells growth via regulating the transcription factors expression of c-Fos and c-Jun.
Fragile histidine triad (FHIT) is a suppressor gene related to cervical cancer through CpG island hypermethylation. Folate is a water-soluble B-vitamin and an important cofactor in one-carbon metabolism. It may play an essential role in cervical lesions through effects on DNA methylation. The purpose of this study was to observe effects of folate and FHIT methylation and HPV 16 on cervical cancer progression. In this study, DNA methylation of FHIT, serum folate level and HPV16 status were measured using methylation-specific polymerase chain reaction (MSP), radioimmunoassay (RIA) and polymerase chain reaction (PCR), respectively, in 310 women with a diagnosis of normal cervix (NC, n=109), cervical intraepithelial neoplasia (CIN, n=101) and squamous cell carcinoma of the cervix (SCC, n=101). There were significant differences in HPV16 status (χ 2 =36.64, P<0.001), CpG island methylation of FHIT (χ
In addition to their fermentable dietary fiber and the soluble β-glucan fiber, oats have unique avenanthramides that have anti-inflammatory and antioxidant properties that reduce coronary heart disease in human clinical trials. We hypothesized that oat consumption will increase insulin sensitivity, reduce body fat, and improve health span in Caenorhabditis elegans through a mechanism involving the daf-2 gene, which codes for the insulin/insulin-like growth factor-1–like receptor, and that hyperglycemia will attenuate these changes. Caenorhabditis elegans wild type (N2) and the null strains sir-2.1, daf-16, and daf-16/daf-2 were fed Escherichia coli (OP50) and oat flakes (0.5%, 1.0%, or 3%) with and without 2% glucose. Oat feeding decreased intestinal fat deposition in N2, daf-16, or daf-16/daf-2 strains (P < .05); and glucose did not affect intestinal fat deposition response. The N2, daf-16, or sir-2.1 mutant increased the pharyngeal pumping rate (P < .05), a surrogate marker of life span, following oat consumption. Oat consumption increased ckr-1, gcy-8, cpt-1, and cpt-2 mRNA expression in both the N2 and the sir-2.1 mutant, with significantly higher expression in sir-2.1 than in N2 (P < .01). Additional glucose further increased expression 1.5-fold of the 4 genes in N2 (P < .01), decreased the expression of all except cpt-1 in the daf-16 mutant, and reduced mRNA expression of the 4 genes in the daf-16/daf-2 mutant (P < .01). These data suggest that oat consumption reduced fat storage and increased ckr-1, gcy-8, cpt-1, or cpt-2 through the sir-2.1 genetic pathway. Oat consumption may be a beneficial dietary intervention for reducing fat accumulation, augmenting health span, and improving hyperglycemia-impaired lipid metabolism.
Epidemiological studies indicate that the increased consumption of sugars including sucrose and fructose in beverages correlate with the prevalence of obesity, type-2 diabetes, insulin resistance, hyperinsulinemia, hypertriglyceridemia, and hypertension in humans. A few reports suggest that fructose extends lifespan in Saccharomyces cerevisiae. In Anopheles gambiae, fructose, glucose, or glucose plus fructose also extended lifespan. New results presented here suggest that fructose extends lifespan in Caenorhabditis elegans (C. elegans) wild type (N2). C. elegans were fed standard laboratory food source (E. coli OP50), maintained in liquid culture. Experimental groups received additional glucose (111 mM), fructose (55 mM, 111 mM, or 555 mM), sucrose (55 mM, 111 mM, or 555 mM), glucose (167 mM) plus fructose (167 mM) (G&F), or high fructose corn syrup (HFCS, 333 mM). In four replicate experiments, fructose dose-dependently increased mean lifespan at 55 mM or 111 m Min N2, but decreased lifespan at 555 mM (P < 0.001). Sucrose did not affect the lifespan. Glucose reduced lifespan (P < 0.001). Equal amount of G&F or HFCS reduced lifespan (P < 0.0001). Intestinal fat deposition (IFD) was increased at a higher dose of fructose (555 mM), glucose (111 mM), and sucrose (55 mM, 111 mM, and 555 mM). Here we report a biphasic effect of fructose increasing lifespan at lower doses and shortening lifespan at higher doses with an inverse effect on IFD. In view of reports that fructose increases lifespan in yeast, mosquitoes and now nematodes, while decreasing fat deposition (in nematodes) at lower concentrations, further research into the relationship of fructose to lifespan and fat accumulation in vertebrates and mammals is indicated.
Pomegranate juice (PJ) is rich in polyphenols, enzymatic ellagic acid metabolites, and hydroxy‐6H‐benzopyran‐6‐one derivatives. Consumption of pure juice shows antioxidant properties, enhances the growth of probiotic bacteriaand short chain fatty acids, prevents clostridium difficile infections, augments memory function and increases brain activity in humans. To determine the mechanism of action, C. elegans wild type (N2) and daf‐16(mgDf50)I were cultured in 96‐well plates with standard lab food E. coli (OP50), or additional PJ (0.01 ‐ 25%, POM Wonderful, LLC., CA).A dose‐dependent “biphasic” relationship of the estimated probability of lifespan in N2 was 42 days in the control, and increased at a lower doses of PJ (0.01‐1%, P<0.0001) up to day 49 (1%) in the treated group, which was reversed at higher doses of PJ (3, 5, 10 and 25%, P<0.05) that contained 蠅2% sugar. A similar and narrower range of the lifespan was detected in the daf‐16 deficient mutant, which was increased at lower doses (1, 3, and 5%) while reversed at higher doses (10‐25%) (P<0.05). The intestinal fat deposition by Nile Red staining in both strains were dose‐dependently decreased (P<0.05). These data indicate that daf‐16 partially mediated these effects. PJ, with less sugar content, extended lifespan and reduced body fat, and excessive sugar reversed the beneficial effect of low dose PJ in C. elegans model organism.
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