جستجوی مقالات مرتبط با کلیدواژه « Cell Cycle » در نشریات گروه « علوم پایه »

Cancer remains a global health problem, with ovarian cancer ranking fifth among cancers affecting women and the leading cause of cancer-related death in women. There are different types pf ovarian cancer, including Epithelial ovarian cancer, Stromal tumors and Germ cell tumors.  Epithelial ovarian cancer is the most common type that includes several subtypes, including serous carcinoma and mucinous carcinoma. To this end, several factors have been identified to increase your risk of ovarian cancer, including older age, inherited gene changes, family history of ovarian cancer, being overweight or obese, postmenopausal hormone replacement therapy, endometriosis, and never having been pregnant. The current strategies to treat ovarian cancer include surgery, chemotherapy, radiotherapy and targeted therapies, and hormone therapy. Scientists continue to investigate the foundational mechanisms involving cancer development, as well as to find new drugs and metabolites having the capacity to control cancer. Alpha-ketoglutarate (AKG), a critical metabolite in the Krebs cycle involved in cellular energy production and the regulation of gene expression. Recent studies have shown that AKG may have the potential to enhance the efficacy of cancer treatments, by modulating the tumor microenvironment and improving the immune response against cancer cells. This study investigates the effect of AKG on ovarian cancer cells.

SKOV3 cells were obtained from Tehran University and cultured in complete culture medium (RPMI, 10% Fetal bovine serum (FBS), and 1% Penicillin-Streptomycin (Pen/Strep)). To find the proper concentration of AKG, SKOV3 cells were cultures in 96-well plate, and treated with different concentration of AKG (range 20 to 220 µM). After 24 and 48 h, the viability of the cells was determined using MTT assay. Based on the results obtained from viability assay, 200 μM of AKG was selected for the next assessments. To evaluate the effect of AKG on SKOV3 cell proliferation using plotting a growth curve, cells were cultured in the presence (200 μM AKG) and absence of AKG, and counted the number of cells every 24h for one week. To determine the population doubling time (PDT), the cells were cultured in the presence (200 μM AKG) and absence of AKG for 72h, then the cell were collected and the number of living cells was counted using Neubauer Chamber. The PDT was calculated using a related standard method. To assess colony formation potential, the SKOV3 cell were cultured in the presence (200 μM AKG) and absence of AKG. After 7 days, the cells were fixed using 10% formalin solution, then the colonies were stained using crystal violet dye, and the number of colonies were counted using inverted microscope. To investigate the effect of AKG on the migration rate of SKOV3 cells, the cells were cultured in complete medium to reach 85% confluence, then treated with mitomycin (10 μM) for 3h, then Created a scratch in the cell monolayer using a sterile pipette tip. the cells were cultured in the presence (200 μM AKG) and absence of AKG for 3 days. The images of the scratch were taken at regular intervals using a microscope, and the closure of the scratch over time was analyzed. To analyze the cell cycle profile, the SKOV3 cell were cultured in the presence (200 μM AKG) and absence of AKG for 48h. Then, the cells were collected and analyzed using a flow cytometry.

Based on the MTT assay, 200 μM AKG was determined as the proper concentration to investigate other biological behaviors of SKOV3 cells. Colony forming assay showed a decrease in the number and size of colonies in the AKG-treated group (P<0.05). In addition, the cell doubling time increased in the treatment group, indicating slower growth rate (P<0.05). Growth curve analysis confirmed reduced cell growth in treated group. Cell cycle analysis showed a higher percentage of treated cells arrested in S and G1 phases. The scratch assay showed slow cell migration and metastasis in the cells treated with 200 µM AKG.

In conclusion, AKG has an inhibitory effect on the proliferation, viability, migration in SKOV3 ovarian cancer cells, highlighting its potential as an adjuvant treatment with existing therapies. More research is necessary to fully investigate the therapeutic effect of AKG in ovarian cancer.

Bone is the hardest and one of the most important tissues in the body. In case of bone damage, the current treatments do not completely repair and regenerate the bone. For this reason, cell-based tissue engineering strategies, especially Mesenchymal Stem Cells (MSCs), have received attention. MSCs have the ability to self-renew and differentiate into different cell types, including bone cells, cartilage cells, and fat cells, among others. They are found in various tissues throughout the body, including bone marrow, adipose tissue, and umbilical cord tissue. Today, MSCs are a valuable resource for regenerative medicine and tissue engineering applications. In addition to the cells, scaffolds are another essential element of tissue engineering. One of these scaffolds is decellularized tissue-derived hydrogels, which are three-dimensional network of hydrophilic polymer chains that can absorb and retain a significant amount of water. In tissue engineering, they mimic the natural extracellular matrix of tissues, providing a suitable environment for cells to attach, proliferate, and differentiate. In the current study, we aimed to investigate the effects of decellularized skeletal muscle-derived hydrogel, known as Myogel, on bone marrow-derived MSCs biological behaviors, including proliferation, viability and migration. In this study, MSCs were isolated from tibia and femur of adult Wistar rats. MSCs were cultured in a complete medium (a-MEM containing 15% fetal bovine serum (FBS) and 1% penicillin/streptomycin (Pen/Strep)). The identity of cells was determined by morphology (using inverted microscope) and expression of specific CD markers (using Flowcytometry). Skeletal muscle was decellularized and accuracy of decellularization was evaluated using special staining. Then Myogel was prepared from digested decellularized skeletal muscle. Here, Myogel substrate was used as the control group, gelatin substrate as the positive control, and un-coated plates as the negative control. The effect of Myogel on survival (MTT method), proliferation (drawing the growth curve and calculating the doubling time of the cell population), cell cycle profile (flow cytometry method), and cell migration (scratch method) were investigated. The MTT test showed that the survival of MSCs in Myogel substrate with a concentration of 0.2 mg/ml was higher than the survival of MSCs in gelatin substrate with a concentration of 0.1 mg/ml and the survival of MSCs in gelatin was higher than the survival of control MSCs. Myogel substrate increased the proliferation and migration of cells and decreased the doubling time of MSCs population. Examining the cell cycle profile showed that a high percentage of cells cultured on Myogel were in the G1 and S phase of the cell cycle, indicating an increase in cell division speed by gelatin and, in the next degree, by Myogel. Therefore, Myogel can be used as a suitable substrate to increase the proliferative and migratory potential of MSCs, which are an important factor in tissue engineering.

Breast cancer is the most common cause of death from cancer among women. The triple-negative breast cancer (TNBC) is the most invasive subtype, and chemotherapy is the only therapy option. Cancer cells preferably utilize the glycolysis pathway even with proper oxygen availability, and this activation plays a great role in tumorigenesis. Therefore, glycolysis targeting can be an effective strategy for cancer treatment. Here, the apoptotic effect of a glycolysis inhibitor named dichloroacetate (DCA) on TNBC cells MDA-MB-231 was assessed, and the expression of anti-apoptotic genes and oncogenic miRNAs was evaluated. MTT assay showed that DCA reduces cell viability in a dose-dependent manner with the IC50 concentration of 50 mM. Annexin/PI assay demonstrated that DCA due to DCA treatment. Finally, the expression of anti-apoptotic genes Bcl2l1 and Mcl1 and oncogenic miRNAs miR21 and miR27a decreased due to DCA treatment. Our results confirmed that DCA, as a glycolysis inhibitor, leads to apoptosis induction in TNBC cells because of reducing expression of viability genes and miRNAs.

Cancer is the result of the overgrowth of malignant cells that have the ability to spread to other parts of the body. Dichloroacetate (DCA) has been considered as a new drug to control various cancers. The effects of stem cells or their conditioned media (CM) on the treatment or control of some cancers have also been shown. In this study, human adipose-derived mesenchymal stem cells (h-ADMSCs) and breast cancer cell line 4T1 were first treatedwith different concentrations of DCA and their viability was assessed by MTT assay and 1mM were selected for CM collection. h-ADMSCs with four groups including groups with no FBS media, ± DCA (-FBS /±1mM DCA) and groups with 5% FBS ± DCA (+5%FBS/±1mMDCA) were treated to prepare CM. Then the viability, colony forming potential, cell cycle profile and apoptosis of CM-treated 4T1 cells were investigated. The results showed that CM in the -FBS/+DCA group decreased the viability (P-Value <0.05) and increased the proliferation of 4T1 cells, compared to the -FBS/-DCA group, respectively. Compared to +5%FBS/-DCA group, CM of +5% FBS/+DCA were able to increase viability and proliferation of 4T1 cells. Also, CM of the four studied groups caused changes in the rate of apoptosis and cell cycle profile of 4T1 cells. It seems that, DCA can increase the viability and proliferation of 4T1 breast cancer cells by affecting on thecomposition of mesenchymal stem cells CM.

Lung cancer is one of the most common types of cancer in the world and Iran. Herbs are a source of a variety of antioxidant compounds that can be used to produce anti-cancer drugs. In the present study, the effect of cytotoxicity of essential oil and hydroalcoholic extract of Juniperus excelsa on A549 lung cancer cells was investigated. The branches of male rootstocks of Aras plant were collected from Chehel Cheshmeh in Firoozkooh and Sirachal in Karaj and the essential oil and extract were prepared by Clevenger and soaking methods, respectively. The degree of cytotoxicity, different concentrations of essential oil and extract of the two regions, on A549 cells in three times of 24, 48, and 72 hours Was evaluated using MTT method. Flow cytometry was used to evaluate cell death and cell cycle in cells treated for 72 hours with 10 µg/ml of essential oil and extract of two regions. The results of cytotoxicity showed that the lethal power of extracts was significantly higher than essential oils, but there was no significant difference between different regions (P <0.01). Also, a further decrease in the number of viable cells and an increase in cell entry into the Sub G1 phase, resulting in an increase in apoptosis treated with male root extract, was proven. Thus, the extract of the branches of this plant has anti-cancer properties by stopping the cell cycle in the G2 / M stage.

Astrocytes are the most important and abundant cells helping neurons. They are involved in the neural survival, ionic, and osmotic homeostasis, as well as in the formation of synapses and growth of the axons and dendrites. Activating markers of the cell cycle increased in Alzheimer’s disease. Cyclin dependent kinase 1(Cdk1) and cyclin E2 (CE2) are among the cell cycle markers. Besides, methamphetamine in non-toxic dose reduces the automatic division capacity and leads to cell differentiation. In this study, the human astrocytes exposed to amyloid beta (Aβ) and treated with low doses of methamphetamine (METH) and the cell cycle arrest and expression of the Cdk1 and CE2 were assessed in all groups. Five groups were used: 1- The cells expose to Aβ, 2- The cells exposed to METH, 3- The cells exposed to Aβ and then METH, 4- the cells exposed to METH and then Aβ, 5- The control group. Each group was repeated three times. Cdk1 gene expression decreased in group 3, treatment group, but increased in group 4, prevention group. The CE2 gene expression decreased in both groups. Furthermore, the cell cycle arrest in G1, G2, and S were assessed. In the Group 3, treatment group, G2 decreased; but in group 4, prevention group, it increased. Changes in the cell cycle are the early symptoms of Alzheimer’s disease. The low dose of METH can reduce cell cycle activating markers as well as reducing cell division and leading the cells to death.

The aim of this study was to compare the effects of chloroform extract of two types of red and brown algae on proliferation, cell cycle and induction of apoptosis in breast cancer cell line.

In this experimental study, MCF7 cancer cell line and normal MRC5 cell line were cultured and then the cells were treated with different concentrations of chloroform extract of algae for 48 hours. Cell survival percentage was calculated by MTT method and type of cell death and cell cycle arrest was assessed by flow cytometry. The results were evaluated by Prism software.

The results showed that both brown and red algae reduced the proliferation of MCF7 cancer line as a concentration-dependent pattern. The IC50 concentration was 88 μg/ml for brown algae chloroform extract and 107 μg/ml for red algae. These values indicated more inhibitory effects of brown algae (63.31%) than red (58.33%). Also, these two extracts effectively induced apoptosis and stopped the cell cycle in G0/G1 stage.

This study showed that the chloroform extract of these algae can be considered as a strong inhibitor for breast cancer.

This study was performed to evaluate the cytotoxic effects of hydroalcoholic extract of Artemisia sieberi and its effect on the cell cycle in the SKBr3 breast cancer cell line.

In this study, hydroalcoholic extract of Artemisia was prepared. SKBr3 cells were exposed to different concentrations (1, 10, 100, 1000 µgml-1) of extract at two different time intervals of 24 and 48 h. We employed MTT assay and flow cytometry analysis to evaluate effects of the prepared extract on the cell cycle characteristics and its cytotoxic properties.

Based on the data obtained from the MTT test, the highest toxicity of the extract observed at the concentration of 1000 µgml-1 within 48 h after the extract exposure. The IC50 of hydroalcoholic extract was 150 and 50 µgml-1 at 24 and 48 h, respectively. According to the data obtained from flow cytometry analysis, the extract arrests cell cycle in 24 and 48 h treatment groups.

The hydroalcoholic extract of Artemisia at certain concentrations inhibits the growth of SKBr3 breast cancer cells by ceasing cell cycle step.

In this study, the effects of recombinant human growth hormone and Gemcitabine alone and in combination with each other were investigated on the lung fibroblast cell lines.

Human growth hormone at 10-400 ng/ml and Gemcitabine at 1-100 μg/ml concentrations were treated with the human lung fibroblast cells and the analysis were performed with MTT assay, propidium iodide staining and scratch assay.

Studies of the cell cycle and MTT assay revealed the effect of growth hormone on the progression of the cell cycle and exit of G1 phase and the cell proliferation, and the inhibitory effects of the cell cycle and growth process by Gemcitabin compared with the control sample. The results of the scratch test indicated that the growth hormone at its effective concentrations caused increased the cell migration compared to control, while the Gemcitabin reduced the migration of the cell to the control.

Using growth hormone in combination to gemcitabin during chemotherapy treatment, it seems that we can reduce the rate of the neem normal cells death. Since these cells are more sensitive to growth hormone´s effect than cancer cells.

HIF-1 transcription factor is a key determinant of oxygen-dependent gene regulation, which its role has been demonstrated for the survival and progress of cancer tumors. The effect of suppression of HIF-1α on the evaluation of HIF-1 dependent processes and interference with pathophysiological events caused by hypoxia is important. The aim of this study was the apoptosis induction in glioma cells by downregulation of Hif-1α gene. In this experimental study, a specific siRNA against the HIF1α gene was developed using OligoWalk and Mit (siRNA.wi.mit.edu) servers and the online design department of Invivogene and Qiagene companies and the efficacy of its silencing in the U87 glioma cell line was quantitatively investigated by the Real-time PCR technique. In order to find out the effect of reduction of expression in the process of cell cycle and apoptosis, staining with PI and Annexin-PI was performed and the number of cells in each phase and the rate of cell mortality with control were compared by flow cytometry. The designed HIF-1a-siRNA was able to reduce HIF1α expression by 40%. The treatment of U87 cells after 24 hours increased the cells by 6% and after 48 hours, increased them by 12% in the sub G1 stage. Confirming the cell cycle changes, 48-hour treatment induced apoptosis in 58% of cells; regarding the 1.5% rate of apoptosis in the control cells, this cell death rate was very significant and showed the ability of the designed siRNA to induce apoptosis. The apoptosis induction of specific siRNA designed against HIF1α gene has a significant effect on the reduction of HIF-1α gene expression, cell growth, and apoptosis.

Stem cells are undifferentiated pluripotent cells, can produce different tissues and organs of the body. Stem cells have two features, self-renewal and differentiation. Of the most important adult stem cells are mesenchymal stem cells. These cells are capable of proliferation and differentiation with induction in the presence of variety of growth factors. Since the placenta extract contains a large amount of VEGF, therefore placenta extract was used to induce the differentiation of omentum mesenchymal stem cells.
The omentum mesenchymal stem cells were separated and cultured and cell-specific markers CD90, CD44, CD73, CD105 and CD34 markers were tested by flowcytometry on them. The extract of the placenta was prepared and after the MTT test, we selected a 20% viability percentage. After 21 days the presence of mesenchymal stem cells omentum in medium and 20 percent of placenta extract, mesenchymal cells were differentiated into progenitor endothelial cells. The expression of CD90, CD73 and CD105 markers was negative and expression of CD31, FLK1 and CD34 markers was positive. G1 phase of the cell cycle in 2st week of prolonged, compared to the control group, this result showed that the cells were exited from the proliferative phase into differentiation phase.
Omental mesenchymal cells in adjacent to the placenta extract, differentiate into endothelial progenitor cells.

Breast cancer is one of the major causes of death among women. Therefore, studying the morphology of cancer is necessary. Computer models and simulations may help scientists better understand this disease, and improve current treatments. In this paper, a model of breast cancer based on Cell Cycle is presented. Five states for each cell in a 2D square lattice is considered. The rules for updating the states of the model in the Moore neighborhood are stochastic. The results of our simulations are presented with/without considering immune system. The growth fraction and necrotic fraction are used as output parameters beside a 2-D graphical growth presentation. Moreover, we introduced a new in-vivo study to measure the output parameters by using Tetrazolium chloride. It can be observed that there is an acceptable compatibility between the experimental tests and simulation results.