Cell and Tissue Journal

Abstract Introduction: Breast cancer is the second leading cause of cancer-related mortality in women. Breast cancer is a multi-step process involving various types of cells, and its prevention remains a global challenge. One of the best ways to prevent breast cancer is through early detection. The upregulation of calcium channels is associated with the proliferation and progression of cancer cells, including breast cancer. The calcium channel blockers are a chemically heterogeneous group that prevents the entry of calcium into the muscle cells of blood vessels and the heart. It has been demonstrated that calcium channel blockers exhibit cytotoxic effects on various types of cancer. Doxorubicin is a well-established chemotherapeutic agent used in the treatment of cancer. Two commonly used calcium channel blockers are amlodipine and diltiazem. However, their interactions with common chemotherapeutic agents such as doxorubicin, which face limitations of cardiotoxicity and cellular resistance, have not been fully investigated.
Aims: This study aimed to evaluate the combined effects of two calcium channel blockers, including amlodipine and diltiazem, on doxorubicin cytotoxicity in breast cancer cell lines.
Materials and Methods: Different concentrations of amlodipine and diltiazem were prepared. Their effects were evaluated both alone and in combination with low concentrations of doxorubicin (which showed minimal cytotoxic effects) on cell proliferation and survival of MDA-MB-231 and MCF-7 human breast cancer cell lines at 48 and 72 hours using the MTT assay. The MTT assay is a colorimetric test that assesses cell metabolic activity. It measures the reduction of MTT, a yellow tetrazole, to purple formazan by mitochondrial enzymes in viable cells. The amount of formazan produced is directly proportional to the number of living cells, making it a useful method for evaluating cell viability and proliferation. Apoptosis is a programmed cell death process that plays a critical role in maintaining tissue homeostasis and eliminating damaged or unwanted cells. Caspase-3/7 activity in drug-treated cell lysates was evaluated to assess apoptosis. All tests were performed at least three times. Differences between samples were analyzed using the t-test and one-way ANOVA, and curves were plotted using Microsoft Excel.
Results: The results of this study demonstrated that both amlodipine and diltiazem inhibited the proliferation of MDA-MB-231 and MCF-7 cancer cells in a concentration- and time-dependent manner. Evaluation of caspase-3/7 activity in the cells treated with amlodipine revealed an increase in caspase-3/7 activity in both cell lines, indicating the induction of apoptosis. In cells treated with diltiazem, caspase-3/7 activity was observed only in MCF-7 cells, while the activity of caspase-3/7 in MDA-MB-231 cells was lower than the control group. Investigating the cytotoxic effect of doxorubicin in the presence of amlodipine and diltiazem showed that these drugs interfered with most cytotoxic concentrations of doxorubicin.
Discussion: The results of this study showed that increasing the concentration of amlodipine and diltiazem, as well as extending the treatment duration, caused cell death in both MDA-MB-231 and MCF-7 cell lines. Caspase-3 and -7 act as executioner enzymes in apoptosis (programmed cell death). The increased activity of caspase 3/7 in MDA-MB-231 and MCF-7 cells treated with amlodipine suggests that amlodipine can induce apoptosis through caspase-dependent pathways. Similarly, increased caspase 3/7 activity was observed in MCF-7 cells treated with diltiazem. However, in MDA-MB-231 cells treated with diltiazem, caspase activity was significantly lower compared to the control group. This unexpected result may indicate that diltiazem induces cell death independently of caspase 3/7 in this cell line, but further experiments are needed to definitively confirm this hypothesis. Calcium is an important regulator of many essential cellular functions and generally acts as a mitogen to stimulate growth in most proliferating cells. It has been reported that tumors typically have abnormally high calcium levels, due to excessive influx of extracellular calcium or the ability of cancerous mitochondria to maintain higher calcium concentrations.  The high levels of intracellular calcium production may activate the calcium second messenger cascade, promoting the overgrowth of certain malignant cells. Human breast cancer cell lines HT-39 and MCF-7, the human promyelocytic leukemia cell line HL-60, and the leukemia cell line L1210, have shown calcium-dependent proliferation. Okazaki et al.  confirmed these findings and demonstrated that the HL-60 cells grow in a manner dependent on extracellular calcium. Additionally, Yonda et al. showed that the growth of a breast cancer cell line (VX2) is tightly regulated by extracellular calcium levels. However, other studies have that removing calcium from the growth medium of some tumorigenic cell lines, such as transformed fibroblasts, hepatic hematomas, mouse embryonic 3T3 cells, and human ovarian cells, does not affect their growth. Therefore, the role of calcium in cell death and proliferation is complicated. Doxorubicin is a widely used chemotherapy drug for breast cancer. Given the high prevalence of hypertension worldwide, cancer patients undergoing chemotherapy often use calcium channel blockers like amlodipine and diltiazem to control blood pressure. Given that amlodipine and diltiazem can induce cancer cell death by blocking calcium channels, this study investigated the cytotoxic effect of doxorubicin in the presence of low concentrations of these drugs on both cell lines. The results showed that amlodipine significantly affected the cytotoxic effect of doxorubicin. This effect depends on concentration and treatment duration. At lower concentrations, amlodipine reduced doxorubicin-induced cell death, and at higher concentrations, due to increased doxorubicin levels, it could not inhibit the drug's toxic effects. Diltiazem is another calcium channel blocker used to lower blood pressure. It has been reported that diltiazem is less potent in lowering blood pressure than amlodipine. Diltiazem also had similar effects to amlodipine. It had antagonistic effects on doxorubicin cytotoxicity at different concentrations and depending on the duration of treatment. Diltiazem, a calcium channel blocker, is known as a P-gp (P-glycoprotein) inhibitor, which reduces cardiotoxicity caused by chemotherapeutic agents. Further studies are needed to explore the underlying mechanisms and therapeutic implications of these findings.
Conclusion: Amlodipine and diltiazem not only induce cell death in cancer cells but also interfere with the cytotoxic effects of doxorubicin at low concentrations. These results highlight the importance of investigating drug interactions between calcium channel blockers and chemotherapeutic agents.

Abstract Introduction: Breast cancer is the most important and widespread type of cancer in women's population.
Aim:This study was conducted to synthesize zinc oxide nanoparticles conjugated with gingerol (ZnO@CPTMS-Gingerol) and evaluate their anticancer effects on breast cancer cells.
Materials and Methods: To synthesize ZnO@CPTMS-Gingerol nanoparticles, one gram of ZnO@CPTMS nanoparticles was dispersed in 30 ml of dry toluene. One gram of gingerol and 10 ml of triethylamine were added to the reaction mixture and refluxed for 24 hours. The product was washed twice with a mixture of distilled water and ethanol (1:1), and the final product was dried at 100°C for 24 hours. Physicochemical properties of ZnO@CPTMS-Gingerol nanoparticles were studied by FT-IR, XRD, DLS, EDS, zeta potential measurement, and electron microscope imaging. The inhibitory effects of different concentrations of ZnO@CPTMS-Gingerol nanoparticles on MCF-7 breast cancer cells and HEK293, as normal cells, were evaluated by the MTT test. To perform this experiment, cells were prepared in 96-well cell culture plates with a density of 104 cells/well, and then were treated with concentrations of 15.625, 31.25, 62.5, 125, 250, and 500 μg/mL of ZnO@CPTMS-Gingerol. After incubating the cells for 24 hours at 37°C, 0.2 ml of MTT solution was added to each well. The wells without nanoparticles treatment were considered as controls. After incubation for 4 hours, the supernatant was removed, and 100 μl of DMSO solution was added to each well. After pipetting, the optical density was read at 570 nm using an ELISA Reader. To determine the percentage of apoptotic and necrotic cells, 5x10⁵ cells were treated with ZnO@CPTMS-Gingerol nanoparticles for 24 hours with half inhibitory concentration (IC50). Then, the treated and control cells were stained with annexin V and propidium iodide (PI) dyes. Finally, cell analysis was done by a flow cytometer. Data analysis was done using device software and dividing the points recorded in the two-dimensional curve into four regions including Q1 to Q4. The experiments were performed in three replicates, and the results were expressed as mean ± standard deviation. Statistical analysis including t-tests, and one-way ANOVA was performed using SPSS. A p

Abstract Introduction: Metal nanoparticles exhibit a broad range of properties and have made substantial contributions to the field of biomedicine, particularly concerning targeted drug delivery systems. These nanoparticles function effectively as carriers for a variety of therapeutic agents, including but not limited to antibodies, nucleic acids, chemotherapeutic agents, and peptides. Metals such as silver, gold, zinc, copper, and cerium display remarkable optical characteristics that augment their functional capabilities. Furthermore, their surfaces can be readily modified via hydrogen bonding, covalent bonding, or electrostatic interactions, facilitating their application with bioactive molecules for specific targeting endeavors. The advancement of numerous nanomedicines aimed at tumor treatment has underscored the potential of cerium oxide nanoparticles (CONPs) as a viable therapeutic agent in oncological therapy. Empirical studies suggest that CONPs possess cytotoxic properties against neoplastic cells, inhibit their invasiveness, and enhance their susceptibility to radiation and chemotherapeutic interventions. Additionally, CONPs exhibit minimal toxicity to healthy tissues and contribute to the reduction of reactive oxygen species (ROS) production. Xanthium strumarium, despite its high toxicity, is acknowledged for its medicinal properties. All constituents of the plant contain toxic compounds in varying concentrations and are utilized in the treatment of various ailments, including malaria, cancer, rheumatism, arthritis, tuberculosis, and respiratory allergies, in addition to their analgesic effects. Its roots, fruits, leaves, and other aerial parts possess significant medicinal value. The technique of green synthesis, which employs natural extracts, is utilized for the production of metal or metal oxide nanoparticles.
Aim:The objective of this research is to examine the impact of cerium oxide nanoparticles synthesized through sol-gel and green synthesis techniques utilizing Xanthium strumarium extract on MDA-MB-231 cancer cells.
Materials and Methods: For the green synthesis approach, Zardineh plants, specifically Xanthium classified under the strumarium category with the ALUH 38785 code, were collected from regions adjacent to the Alborz mountains. The leaves of the plant were separated and ground into a fine powder. The resulting powder was extracted and purified using a reflux method. This extract served as a reducing agent for cerium nitrate metal ions. In the sol-gel method, cerium nitrate and cetyltrimethylammonium bromide were used. Characterization of the nanoparticles was conducted using FTIR, EDAX, SEM, and AFM techniques. Furthermore, the MTT assay was used to assess and compare the cytotoxic effects of cerium oxide nanoparticles synthesized on MDA-MB-231 cancerous cells.
Results: AFM analysis indicated that the size of the green synthesized nanoparticles was 10 and Sol-gel method nanoparticles were 13 nm. SEM and EDAX analysis revealed that the synthesized cerium nanoparticles exhibited a nearly spherical shape, with those produced via the sol-gel method showing uniform accumulation and dispersion. The MTT assay results demonstrated that the cytotoxic effect of cerium oxide nanoparticles synthesized on MDA-MB-231 cancerous cells increased with both time and concentration. Notably, the lethal effect of nanoparticles synthesized through the green method was found to be more pronounced than nanoparticles produced via the sol-gel method.
Conclusion: Cerium oxide nanoparticles (CONPs) exert toxicity in cancerous cells, inhibit invasion, and enhance the sensitivity of cancerous cells to radiotherapy and chemotherapy. The green synthesis method uses biological extracts, such as plant materials, in place of industrial chemical agents to reduce metal ions and generate valuable nanoparticles. This approach offers several advantages over traditional chemical synthesis, including cost-effectiveness, reduced environmental pollution, and improved safety for both the environment and human health.

Abstract Aim: Breast cancer remains a significant health challenge, being one of the most common cancers among women and a leading cause of cancer-related deaths globally. The need for effective treatment options is paramount, and recent research has spotlighted sulfonamide derivatives for their notable antitumor properties. These compounds have shown considerable cytotoxic effects against various cancer cell lines, including breast cancer, through mechanisms such as apoptosis induction and inhibition of heat shock protein 70 (HSP70), which is crucial for cancer cell survival. This study focuses on synthesizing a solid lipid nanocarrier that incorporates a sulfonamide derivative, aiming to enhance its anticancer efficacy against the MCF-7 breast cancer cell line. The encapsulation of sulfonamide within these nanoparticles is expected to improve its bioavailability by increasing solubility and stability, thereby allowing higher concentrations to effectively reach tumor sites. Additionally, these nanoparticles are designed to minimize systemic toxicity and protect healthy tissues from adverse effects, resulting in enhanced therapeutic efficacy.
methods: The research involved synthesizing solid lipid nanoparticles (SLNs) containing the sulfonamide derivative, followed by a comprehensive analysis of their physicochemical properties. Key parameters assessed included drug loading capacity, morphology, size distribution, and release profile using techniques such as Fourier Transform Infrared Spectroscopy (FTIR), Dynamic Light Scattering (DLS), Atomic Force Microscopy (AFM), and dialysis methods. The cytotoxicity of the nanocarrier was evaluated on MCF-7 cells through the MTT assay, alongside assessments of cell proliferation and migration using scratch assays.
Results: The synthesized nanocarrier had an average size of 315 nanometers with a Polydispersity Index (PDI) of 0.3, indicating good uniformity. AFM analysis confirmed its spherical morphology. The nanocarrier demonstrated a high drug loading capacity of approximately 82% for the sulfonamide derivative and facilitated a controlled release over time. Cytotoxicity assays revealed that while the blank nanocarrier was safe, the formulation containing the sulfonamide derivative exhibited significantly enhanced cytotoxic effects on MCF-7 cells at lower concentrations compared to the free sulfonamide alone. This improvement in efficacy is attributed to the controlled release mechanism that allows for sustained exposure of cancer cells to the active compound. Moreover, the nanocarrier was more effective in inhibiting both growth and migration of cancer cells than treatments with free sulfonamide, as evidenced by scratch assays.
Conclusion: This research highlights the potential of solid lipid nanoparticles in improving the therapeutic effectiveness of sulfonamide derivatives against breast cancer. The synthesized nanocarrier demonstrates favorable physicochemical properties, including high drug loading capacity and controlled release, which are essential for effective treatment outcomes. Notably, encapsulating sulfonamide derivatives significantly enhances cytotoxicity against MCF-7 cells at lower doses compared to their unencapsulated counterparts, emphasizing its promise for improved therapeutic strategies. Furthermore, these nanoparticles effectively inhibit cell proliferation and migration, contributing to tumor growth suppression. This innovative approach aims not only to enhance treatment efficacy but also to minimize systemic toxicity and protect healthy tissues from adverse effects. Future research should focus on innovative clinical applications and further optimization of these nanocarriers to maximize their potential in oncology, paving the way for more effective treatments for breast cancer.

Abstract Aim:: The renin-angiotensin system (RAS) is an endocrine system essential for regulating blood pressure and fluid balance. Components of this system are expressed not only in various body cells but also in breast cancer cells. Angiotensin-converting enzyme (ACE) inhibitors, which are widely used as antihypertensive agents, have been proposed to have an additional benefit in reducing the risk of certain cancers. Doxorubicin is a commonly used chemotherapy drug, also employed in the treatment of breast cancer. One of the side effects of doxorubicin is its toxicity to cardiac cells. This research aims to investigate the effect of cytotoxicity of four RAS antagonists (enalapril, captopril, valsartan, and losartan) in the presence and absence of doxorubicin against two breast cancer cell lines including MCF-7 and MDA-MB-231. The study’s objective is to determine whether these RAS inhibitors can modulate the cytotoxicity of doxorubicin and their potential impact on breast cancer cell survival.Material and methods:  MTT is one of the colorimetric methods to investigate cell survival. This assay is based on the conversion of the MTT reagent to a formazan product by metabolically active cells, providing a quantitative measure of cell viability. The effect of RAS inhibitors in the presence and absence of doxorubicin on the survival of cancer cells was measured using the MTT test. Chemotherapy drugs, such as doxorubicin, typically reduce cell survival by inducing apoptosis. One of the markers of apoptosis induction in cells is the evaluation of caspase-3/7 activity. The induction of apoptosis in MDA-MB-231 cells treated with the RAS inhibitors was investigated using a caspase-3/7 activity assay kit, which quantifies the enzymatic activity in cell lysates. Results: Enalapril had no significant cytotoxic effect on breast cancer cells at concentrations up to 500 μg/mL. Captopril and losartan were toxic to breast cancer cells. Valsartan had no cytotoxic effect on breast cancer cells and increased cell proliferation over time. The cytotoxic effects of captopril and losartan on breast cancer cells may be attributed to their inhibitory effects on the RAS. The RAS plays a crucial role in regulating blood pressure and fluid balance, but it also has inhibitory effects on tumor growth and progression. By blocking the activity of the RAS with captopril and losartan, the cells may experience reduced proliferation and ultimately cytotoxicity. Enalapril, captopril, valsartan, and losartan protected breast cancer cells from doxorubicin cytotoxicity in a concentration- and time-dependent manner. Captopril and losartan treatment increased caspase-7/3 activity in MDA-MB-231 cells. The increase in caspase-7/3 activity in MDA-MB-231 cells suggests that captopril and losartan-induced cytotoxicity may be accompanied by apoptosis. Apoptosis is a desirable outcome in cancer treatment as it allows for the elimination of cancer cells while preserving normal tissue function.
Conclusion: RAS inhibitors can interfere with the cytotoxic effects of doxorubicin on breast cancer cells, depending on the concentration and duration of exposure. Further research is required to understand the optimal use and dosage of RAS system inhibitors in this context to ensure a balance between protecting the heart from doxorubicin-induced cardiotoxicity and maintaining the efficacy of cancer treatment.
 

Abstract Aim: Nowadays, one of the great challenges of mankind is to find a suitable way for the treatment of cancer. Recent developments show that nanotechnology has a significant impact on the prevention, diagnosis and treatment of cancer. In nanotechnology, there are different physical and chemical methods to produce nanoparticles but mostly chemical methods are used. The nanoparticles produced using these methods are harmful to health due to the absorption of chemical species on their surface. In order to eliminate this big problem, biological methods such as the use of fungi, bacteria and plants have replaced other methods for the synthesis of nanoparticles which is called green synthesis. It is cheaper, simpler and non-toxic than other methods. The use of plants for the synthesis of nanoparticles has become more important than other biological methods due to the elimination of the difficult step of cell culture maintenance.
Material and Methods: In this study, gold nanoparticles were formed after treating the HAuCl₄ solution with the aqueous extract of Anarijeh plant with the scientific name Pimpinella affinis. In this research, different amounts of aqueous extracts of leaves and stems of Pimpinella affinis were used for the synthesis of gold nanoparticles. UV-Visible spectroscopy and DLS methods were used to evaluate nanoparticles and determine their average size and stability. Also, SEM method was used to investigate their morphology. FTIR method was used to determine the functional groups of the aqueous extract and synthesized gold nanoparticles; in addition GC/MS device was used to determine the composition of the extract. Finally, MTT analysis was used to investigate the cytotoxic effects of nanoparticles on MCF-7 cell line along with treatments of 24, 48 and 72 hours.
Results: The results of the analysis were showed that the optimal concentration of the Pimpinella affinis extract for the synthesis of gold nanoparticles is 1 mg/ml. The synthesized gold nanoparticles using the mentioned concentration of the extract have an average size of 20 nanometers with a zeta potential of -61 mV which has the best stability. They had a spherical shape with a polydispersity equal to 0.7. The results of FTIR analysis show the presence of hydroxyl, simple carbonyl groups and hydrocarbon functional groups in the compounds of the extract. Experiments showed that phenolic and carboxylic compounds play the most important role in the reduction of gold salt. Also, proteins and lipids have made gold nanoparticles stable. The essential compounds identified in the extract by GC/MS method include Phenolic and flavonoid compounds and terpenes which are confirmed by the FTIR spectrum. The treatment time of 48 hours for MCF-7 cell line is the best time for the toxicity of nanoparticles with IC50 equal to 384.2 µg/ml, which was determined by MTT analysis.
Conclusion: According to the above findings, it can be concluded that Pimpinella affinis is one of the suitable options for the synthesis of gold nanoparticles, and it can be done with more studies on nanoparticles synthesized using this plant, considered it as one of the efficient methods to achieve the goal of proper treatment for breast cancer.

Abstract Aim: Nowadays, much attention is paid to the effects of natural factors on physiological and pathological processes in human body. In this regard, lack of oxygen or hypoxia is one of the crucial biological factors involved in various physiological processes such as wound healing and pathological processes such as cancer. Moreover, it is very important to find natural compounds affecting the characteristics and functions of cells. Thymoquinone (TQ) is a natural compound derived from certain plants such as Nigella Sativa. It has many biopharmacological effects, including anti-bacterial, anti-oxidant, anti-inflammatory, anti-diabetic, anti-aging, anti-cancer, etc. Given the biopharmacological properties of TQ and the importance of hypoxia as an important factor affecting physiological and pathological processes, this study was designed to investigate the effect of TQ under cobalt (II) chloride-mediated hypoxia on breast cancer and wound healing by evaluating the expression of SOX2, CDK4, c-MET, and DNMT1 genes in a breast cancer cell line (MCF7) and a normal fibroblastic cell line (HDF) that treated with these compounds.
Materials and Methods: In the present study, after the cultivation of MCF7 and HDF cell lines, each of the cells were divided into two groups. The treatment group was treated simultaneously with 500 ng/ml of TQ and 100 μM of cobalt (II) chloride for 24 h and the control group was only treated with cobalt (II) chloride. After incubation time, total RNA extraction, DNase I treatment, and cDNA synthesis were carried out and finally, the expression of target genes was examined by real-time PCR assay. In this study, relative threshold method was used to determine the amount of gene expression changes, and SPSS software and Student's t-test statistical method were used to find the significance of gene expression changes in the treated groups compared to the controls.
Results: The results showed that simultaneous treatment of MCF7 cells with TQ and cobalt (II) chloride significantly (P < 0.05) reduced the expression of CDK4, c-MET, and DNMT1 genes at about 4.35-, 1.89-, and 2.08-fold, respectively, compared to the control group. However, the treatment of MCF7 cells caused a limited increase in the expression of SOX2 at about 1.14-fold, which was not significant according to the significance level of ≥ 1.5. Moreover, simultaneous treatment of HDF cells with TQ and cobalt (II) chloride significantly increased c-MET gene expression by about 1.86-fold. In addition, the treatment of HDF cells caused a slight increase in the expression of CDK4 at about 1.26-fold, which was not significant according to the significance level of ≥ 1.5. Also, the expression of SOX2 and DNMT1 genes has decreased at about 1.28- and 1.32-fold in the treatment group compared to the control group, which were as not significant according to the significance level of  ≥ 1.5.
Conclusion: Overall, it can be concluded that TQ under cobalt (II) chloride-mediated hypoxia may inhibit breast cancer by inhibiting the expression of genes involved in proliferation and migration. In addition, due to the important role of fibroblasts in the wound healing process, TQ may help wound healing under hypoxic conditions by increasing the migration potential of fibroblast cells.

Abstract Aim: The three-dimensional (3D) culture of cancer cells is a method that provides the possibility for growth and comprehensive communication of cells in a 3D space, leading to the generation of tumorspheres. In recent years, developing tumor models from cancer cells by using the 3D cell culture method has attracted a lot of attention because it has been introduced as an accurate and reliable strategy for studying cancer stem cells (CSCs) and CSC-based therapeutics. The 3D tumor models in comparison to the monolayer culture (two-dimensional (2D) culture) of cells more resemble in vivo conditions. Because in tumor models, the tumor microenvironment, cell to cell and cell to extracellular matrix interactions and hypoxia condition, which is necessary for the survival of CSCs, are well reproduced. Through the use of several types of cells, including cancer and stromal cells, tumor models have the ability to develop and reflect the complexity of the tissue of interest, which in such a case, are even more accurate models in reflecting the biochemical and physical conditions of the body. Therefore, in the present study, the 3D model of breast cancer has been constructed with the aim of investigating the relationship between the cell behavior and the cell culture conditions (2D and 3D), and a comparative study of the growth and drug response of the two human breast cancer cell lines; MCF-7, and MDA-MB-231. Material and Methods: The two breast cancer cell lines, MCF-7, and MDA-MB-231, were cultured in 2D and 3D (in two modes; on top and embedded) on the Matrigel-based scaffold. The molecular phenotype of cells based on surface markers was examined by flow cytometry. Mammosphere growth was followed in 12 days and their growth kinetics was determined. To evaluate the drug response of cells, two anticancer drugs; actinomycin D and paclitaxel were applied. Primarily, the IC50 values of the two drugs were evaluated, then the generated mammospheres were treated at the indicated dose of the drugs, and their effect on the growth of the mammospheres was followed.
Results: The MCF-7 and MDA-MB-231 cell lines cultured in 2 and 3D, showed a significant difference in their molecular phenotypes. So, it seems that the expression of CD44 has significantly decreased.  On the other hand, the growth rate of cells in two different modes of 3D culture; on to and embedded, is different. Likely, the drug response evaluation shows a significant difference in 2D and 3D culture, so that the inhibitory effect of paclitaxel compared to actinomycin D has decreased in 3D culture. In addition, the results show that MCF-7 and MDA-MB231 have different drug responses, which can be affected by their different molecular phenotypes. Conclusion: The results of the study confirm that the molecular phenotype of cancer cells, their growth, and drug response are strongly affected by the type of the understudied cell lines, the cell culture method, and the applied drug. Consequently, conducting cancer studies as accurately as possible requires obtaining a model that is most similar to the corresponding tumor in the body.
 

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Abstract

Abstract Aim: This research aimed to study the anticancer effects of nano-selenium oxide-enriched Saccharomyces bullardi on DMBA-induced breast cancer cells in rats.
Material and Methods: In order to induce cancer, the carcinogen with a concentration of 60 mg/kg was injected into the left breast nipple of the female rats. When the tumors grew to about 10 mm, the cancerous tumor was isolated from the breast of the animals and used to make tissue sections and individual cells. Cancer cells were treated with different concentrations of S. boulardi suspension and nano-selenium oxide-enriched S. boulardi. The cytotoxicity assay was performed with two methods of MTT and Trypan blue staining.
Results: Comparison between two cell groups treated with S. boulardii and nano-selenium oxide-enriched S. boulardi using two tests, it was found that there were significant changes in cancer cells viability in both 0.5,1 µg/ml concentrations. with increasing the concentration, the cancer cell viability was significantly decreased. cell viability in the cell line treated with nano-selenium oxide-enriched S. boulardi yeast, with the increase in the concentration of enriched yeast was decreased. A comparison between the yeast and enriched yeast in different concentrations, revealed that there was a significant difference between cytotoxicity effects of them on the cells.
Conclusion: Probiotic yeasts could be an appropriate candidate for the treatment of some diseases including cancers, especially when combined with selenium compounds.
 

Abstract Aim: The aim of the current work was to investigate the anticancer activities of Zinc Oxide nanoparticles (ZnONPs) through modulation of Glutation peroxidase and Glutationreductase gene expression in breast cancer cells.
Material and Methods: In this investigation, the breast cancer MCF-7 and normal HEK293 cell lines were treated with various concentrations of ZnONPs for overnight. Cell viability was measured using MTT(3-(4, 5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay against cancer and normalcells. The quantity of Glutation peroxidase and Glutationreductase genes compared to GAPDH gene expressions were evaluated using the real time PCR method.
Results:The MTT data showed that ZnONPs significantly decreased the viability of cancer cells compared to normal cells in dose-dependent mode. Moreover, the mRNA levels of Glutation peroxidase and Glutation reductase genes was significantly increased by 2.13±0.07 (p < 0.001) and 1.22±0.05 (p < 0.05) fold, respectively, following treatment withZnONPs.
Conclusion: According to the results of this investigation, the Glutation peroxidase and Glutation reductase gene expression was the key factors of glutathione system in elimination of increasing reactive oxygen species treated with ZnONPs.
 

Abstract Aim: 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.
Material and Methods: 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.
Results: 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.
Conclusion: The hydroalcoholic extract of Artemisia at certain concentrations inhibits the growth of SKBr3 breast cancer cells by ceasing cell cycle step. 
 

Abstract Aim: The aim of this study was purification of magnetosomes of Magnetospirillum gryphiswaldense and investigation cytotoxicity effect of the purified particles of this bacterium on the breast cancer cell lines.
Material and Methods: In this study, the standard strain of bacteria was cultured on DSMZ broth at temperature of 28°C for seven to ten days and incubated under the microaeraphilic conditions. To ensure phenotype tests, the PCR reactions were performed using specific primers (MT1166), associated with scanning electron microscope imaging. The influence of purified magnetosome from Magnetospirillum gryphiswaldense in various concentrations was investigated on the breast cancer cell lines. Kruskalwalis test was performed for statistical analysis.
Results: Gram staining results showed that the bacterium was gram negative spirillum. Electronic micrographs indicated that the magnetosome of this bacterium was 60 nanometer in size. Purified magnetosome from Magnetospirillum gryphiswaldense did not show considerable cytotoxic properties on the breast cancer cell lines. The percentage of living cells against magnetosomes purified from the bacterium Magnetospirillum gryphiswaldense was 85% (p=0.04).
Conclusion: Magnetospirillum gryphiswaldense magnetosomes killed 15% of the cancer cells. The size and structure of magnetosomes of Magnetotactic bacteria are great importance in the elimination of the breast cancer cells.
 

Abstract Aim: In the present study, The anti-metastatic and cytotoxicity effects of cerium oxide nanoparticles on two MCF-7 and T47D breast cancer cell lines have been studied.
Material and methods: MCF-7 and T47D breast cell lines and normal HEK293 cells were treated with 6.5 mg, 650μg, 65μg, 650ng, 65 ng of cerium oxide nanoparticles and MTT analysis was performed to investigate the toxicity of nanoparticles. Then, NM23 and KAI-1 genes expression were measured by real-time PCR method.
Results: Concentrations of 650 μg and 6.5 mg of CNP resulted in approximately 60% death of MCF-7 and T47D cells. Also, in treatment of normal cells with a concentration of 6.5 mg of CNP, Reduced survival of 25% was observed. Gene expression analysis showed that the two anti-metastatic NM23 and KAI-1 genes did not increase expression under  CNP treatment.
Conclusion: According to the results of this study, the cerium oxide nanoparticles have toxic effects on breast cancer cells, However, this effect varies dose and type of cell line dependent. On the other hand, the study of the anti-metastatic expression of genes showed that this nanoparticle is not capable of enhancing the expression of these genes and therefore is ineffective in controlling cell invasion and is likely to exert its anticancer effect through induction of cell death.
 

Abstract Aim: The present study aimed to investigate the effects of aqueous and alcoholic extracts of shallot on breast cancer cells compared to carboplatin and taxol treatments. Material and methods: Different concentrations of drugs taxol and carboplatin and aqueous and alcoholic extracts of shallots were prepared. Using Trypan blue and MTT, cytotoxicity on breast cancer cells, in different times and concentrations were evaluated. Utilized Hoechst and propidum iodide staining morphological changes and possible apoptosis of cells were determined. The data statistically analyzed using one-way analysis of variance and the mean level of P Results: The results indicate that shallot alcoholic extract has more inhibitory effects on cancer cells than aqueous extract at concentration range (0.01 to 0.05 g/L). Also, the simultaneous effect of shallot’s extract, accompaniment with carboplatin, caused enhancement in cytotoxicity of carboplatin. On the other hand, accompaniment of aqueous extract with taxol led to reduction of taxol cytotoxicity. Conclusions: This study showed aqueous and alcoholic extracts of shallots has cytotoxicity effects on breast cancer cells on rats affected by breast cancer. This plant is a herb which can be used against breast cancer  can be subjects for further research.

Abstract Aim: In this article, the ability of p < sup>32 radioactive drugs for treatment and control of breast cancer in rat model and also verifying of distribution of drug in rat organs are investigated.
Material and Methods: 10 to 20 mg per kg of DMBA gavaged to SD strain rats. Tumors 15-10 mm in diameter were selected for testing. P32 radioactive drugs injected to developed tumors with interval 3, 5 and 7 days. The distribution of the P32 radioactive drugs in the body of rat were analyzed by NI detector. After the treatment period, animals were anesthetized and the tumor is completely removed under sterile conditions and placed in 10% formalin. Sections of the tumors were obtained and processed using Tissue Processor. After tissue processing and sectioning, the samples were stained with hematoxylin - eosin were examined.
Results: The results obtained from the examining histological sections prepared from tumor tissue confirmed that, the pathology of tumors induced by DMBA in rats used in this study is very similar to human mammary tumors. Five days after injection, we could find tumor's cells and lymph ducts are covered by residual epithelial cells. Many of the cells are separated from the basement membrane and collapsed into the tubular cavity. Rest of the cells has small nuclei, with chromatin condensation mode and cytoplasm was compact and dense. In radius of about 7-8 mm around the site of injection the tumor's cells were necrosis and formed a cavity, inside of tumor.
Conclusions: These observations showed further penetration and influences of radiation emitted from the phosphor 32 in the tumor tissue based on our injection pattern.
Therefore if given the proper distance of injection within the tumor, destroying the tumor's ability to be on time will be shorter.