جستجوی مقالات مرتبط با کلیدواژه « ژن p53 » در نشریات گروه « زیست شناسی »

 As the second leading cause of death worldwide, cancer has been a long-standing and rapidly evolving focus of biomedical research and practice. Ovarian cancer is one of the deadly malignancies of women, which is known as the "silent killer". Because its symptoms usually appear when the disease has reached advanced stages and is mostly incurable. On the other hand, currently common treatment methods are associated with various limitations, failures and side effects, which have made researchers pay more attention to the compounds extracted from plants as anti-tumor and anti-cancer agents in the last two decades. The studies conducted on the various properties of Ashwagandha (Withanaia somnifera) show that this plant has therapeutic effects and anti-cancer properties that can even be effective on the process of apoptosis mediated by different genes, including P53. Today, P53 is known as a gene It has a key role in all types of cancers and mutations in this gene have been observed in 60% of ovarian cancers. Therefore, the aim of this study is to investigate the cytotoxic effects of the hydroalcoholic extract of Ashwagandha (Withanaia somnifera) and the changes in P53 gene expression in response to this substance in ovarian cancer cells (cell line A2780).

For this purpose, extraction of Ashwagandha plant was done using soaking method. Then, the compounds present in the extract were determined using standard phytochemical tests. Then A2780 cells were treated with different concentrations of Ashwagandha extract for 24, 48 and 72 hours. The effects of this extract on cell survival were evaluated using the MTT test, and IC50 was calculated. Then, A2780 cells were exposed to concentrations of 250 and 500 µg/ml for 24 and 48 hours, and the level of P53 gene expression was investigated by Real-Time PCR. Finally, statistical analysis and data interpretation was done using GraphPad Prism software.

 MTT results showed that Ashwagandha extract at concentrations of 62.5, 125, 250, 500, and 750 µg/ml significantly decreased cell viability in a time- and concentration-dependent manner. The lowest percentage of survival rate is related to the concentration of 750 μg/ml and the time of 72 hours, while the highest percentage is related to the concentration of 62.5 μg/ml and the time of 24 hours. After 24, 48, and 72 hours, respectively, IC50 was obtained at concentrations of 512.6, 339, and 226.6 μg/ml, and Real-Time PCR results showed that the expression of the P53 gene during 24 hours of treatment with concentrations of 250 and 500 μg/ml of extract had increased significantly. Also, increasing the concentration of the extract had a significant effect on the expression of this gene.

 The results of this study indicate the cytotoxic effect of Ashwagandha extract on ovarian cancer cells, and by increasing the expression of the P53 gene, it can induce anti-cancer effects. It is hoped that by knowing the mechanisms of action of this medicinal plant and designing new drugs, it will be possible to stop the progression of ovarian cancer and thus help to increase the life span of these patients against this silent killer.

In this study the effects of paclitaxel and oxaliplatin on colon cancer cell line (HT29) and expression of apoptotic genes caspase 3, 9, and p53 were examined. Using the MTT method, the cytotoxicity of paclitaxel and oxaliplatin and synergic effect at different concentrations on the HT29 cell line was assessed. The IC50 of paclitaxel and oxaliplatin was determined.The expression level of caspase 3 and 9 was assessed using the Real-Time PCR method after the cells had been exposed to the IC50 concentration. Apoptosis of the cells was done using Annexin V/PI and DAPI staining. The treatment of cells revealed that paclitaxel and oxaliplatin at concentrations of 3.25 and 0.00062 µg/ml , respectively, have the most cytotoxic effects and its IC50 value was determined to be 12.5 µg/ml and 0.00016 and treatment groups at concentrations of 3.25 and 0.00062 µg/ml , respectively, decreased the cell viability and its IC50 value was determined to be 12.5 µg/ml and0.00016µg/m. The expression level of caspase 3 and 9 P53 was also increased in the treated colon cancer cell line. DAPI staining showed apoptosis in the simultaneous treatment groups with. Using Annexin V/PI reveals that 98 percent of the cells in the control group are healthy and a considerable number of the cells in the treated groups have undergone apoptosis. Is. It is clear that paclitaxel and oxaliplatin are effective options for treating colon cancer given their cytotoxicity and stimulation of the apoptotic process in colon cancer cell lines.

Ibuprofen, as a drug contaminant, has deleterious and in some cases irreversible effects on aquatic organisms and in general on living things, which in many cases can result in genetic damage and damage to the DNA structure. The effects of different concentrations of ibuprofen on DNA damage and damage to zebrafish are investigated. In this study, genetic changes of p53 gene and its expression in zebrafish after two weeks of exposure to 0.1, 1 and 10 mg / l ibuprofen in vitro were investigated.

In this study zebrafish were exposed to the above mentioned concentrations for two weeks and then RNA extracted from them. The results were analyzed using QPCR method.

The low drug, 0.1 mg / l had no effect on p53 gene expression, while the other two concentrations, which were 1 and 10 mg / l ibuprofen, respectively, showed a significant difference between the control and the drug containing sample. As a result, the p53 gene was highly expressed. Also for the internal control gene that was GAPDH, there was no significant difference at the lowest drug concentration. Ray did not show a significant difference between the treatment and control samples, while in the subsequent treatments there was a significant difference between control and treatment samples.The final result of this study was that p53 gene expression increased 1.09, 0.57 and 2.2 fold in sample with lowest drug concentration, mean concentration and highest drug concentration, respectively.

Colon cancer is the third most common cancer in the world,with nearly 1.4 million new caces diagnosed in 2012. Due to the increased incidence of cancer,the use of new chemotherapy molecules is required.Many studies have shown that intestinal cancers can be treated through natural marine products that contain a large amount of active biological substances with new chemical steractuers and new drug activities. The aim of this study was the evaluation of the hydroalcholic extract of Sargassum ciliforium on HT-29 colorectal cells line and the evaluation of P53 and APC genes expression using Real time PCR Technique.In this study, determination of toxicity of Sargassum ciliforium algae extract with MTT method at 5 different concentrations of 0.001 / 0.01 / 0.1 / 0.1, 10 mg / ml and one control group on cell lines of HT-29 colon cancer and cell line Normal kidney of HEK human embryos was studied. Data analysis was performed using SPSS software and one way ANOVA test. Also, the expression of P53 and APC genes was evaluated using Real time PCR The results showed that Sargassum ciliforium alga extract at a concentration of 10 mg / ml would decrease the biosynthesis of the intestinal cancer cell line in HT-29 human and delay the growth of tumor cells, and the extract of this algae can be used to develop anticancer drugs. The results of real time PCR showed that cell death induced by Sargassum ciliforium alga extract was via activation of APC protein.

Aim and P53 tumor suppressor gene, also known as “genome guardian” is mutated in more than half of all kinds of cancers. P53 protein acts as a tetramer and is a transcription factor, controlling the transcription of genes that are necessary for apoptosis or cell proliferation arrest. Also it inhibits the transcription of genes that are responsible for cell growth. Experimental researches revealed that acidic pH raised the rate of cancer and mutation in 248CGG codon of P53 gene. This may be due to protonation of this three-nucleotide codon. Mutation in this codon changes the encoding amino acid and subsequently produces a protein, which has oncogenic features instead of tumor suppressor characteristics of original p53 protein. In current study, we perform an investigation on the impact of protonation on stability of codon 248CGG in this gene. Molecular mechanic methods used in this study to calculate energy levels. HYPERCHEM software used in AMBER, BIO+, MM+ and OPLS. Obtained results from different force fields all suggest that acidic condition can increase molecular instability in given sequence in comparison with physiological pH. Our results suggested a reliable answer about the effect of protonation on mentioned codon and its stability. From theoretical point of view, acidity can increase the instability of this specific codon. Along with the experimental investigations, our results can, to some extent, elaborate the mutagenesis of acidic pH.