Introduction: Biological scaffolds materials derived from the extracellular matrix (ECM) have bee... more Introduction: Biological scaffolds materials derived from the extracellular matrix (ECM) have been created the most promising evolution in the field of tissue engineering. it seems that a clear understanding of such a matrix and attempt to make them applicable will let us to discover important ...
Breast cancer is the most common cancer in women worldwide. Traditional therapies are expensive a... more Breast cancer is the most common cancer in women worldwide. Traditional therapies are expensive and cause severe side effects. Targeted therapy is a powerful method to circumvent the problems of other therapies. It also allows drugs to localize at predefined targets in a selective manner. Currently, there are several monoclonal antibodies which target breast cancer cell surface markers. However, using antibodies has some limitations. In the last two decades, many investigators have discovered peptides that may be useful to target breast cancer cells. In this article, we provide an overview on anti-breast cancer peptides, their sources and biological activities. We further discuss the pros and cons of using anticancer peptides with further emphasis on how to improve their effectiveness in cancer therapy.
Anti-cancer Agents in Medicinal Chemistry, May 11, 2023
Introduction: Prostate cancer is the second most prevalent cancer among men. Despite different tr... more Introduction: Prostate cancer is the second most prevalent cancer among men. Despite different treatments, including surgery, chemotherapy, radiation therapy, hormone therapy and immunotherapy for this disease, patients ultimately progress to advanced states. Thus, there is a need for new treatment options targeting cell growth and apoptosis to better control the proliferation and metastasis of these cells. There are many reports indicating overexpression of the 15-lipoxygenase-1 (15-LOX-1) enzyme in prostate tumors. Studies have also shown that inhibition of this enzyme prevents the progression of prostate cancer. Objective: This study was conducted to assess the anti-cancer properties of some coumarin derivatives as possible 15- LOX-1 inhibitors, on PC-3 prostate cancer cells. Methods: In this study, the activity of 15-LOX-1 was evaluated in PC-3 cells by a spectrophotometric assay. In addition, due to high similarity between the 15-LOX-1 and soybean 15-lipoxygenase (SLO) (L1; EC 1, 13, 11, 12) active sites, the soybean SLO was used to investigate inhibitory effects of synthetic coumarin compounds 8- isopentenyloxycoumarin (8-IC), 8-isopentenyloxy-3-carboxycoumarin (8-ICC), 8-geranyloxycoumarin (8-GC), 8- geranyloxy-3-carboxycoumarin (8-GCC), and 8-farnesyloxy-3-carboxycoumarin (8-FCC) on this enzyme. Moreover, the cytotoxic and anticancer effects of the coumarin compounds were examined on PC-3 (Prostate Cancer) and HDF-1 (Human Dermal Fibroblast) cells by assay. Finally, apoptosis-inducing effects of alamarBlue all synthetic compounds were determined by flow cytometry. Results: The IC50 values obtained by the alamarBlue test revealed that 8-IC, 8-GC and 8-GCC had cytotoxic effects on PC-3 cells. Treating both PC-3 and HDF-1 cells with 8-ICC and 8-FCC did not significantly reduce cell number. Furthermore, the IC50 values of 8-IC on HDF-1 cells showed cytotoxic effects, while treating these cells with 8-GC and 8- GCC did not show any significant cytotoxicity on these normal human fibroblasts. Assessing the ability of 4-MMPB (as a specific inhibitor of 15-LOX-1), 8-GC, and 8-GCC compounds to inhibit SLO revealed that these compounds exerted strong 15-LOX-1 inhibitory activity, while 8-IC and 8-FCC had a weak inhibitory effect and also 8-ICC showed no inhibitory effect on SLO enzyme. In addition, flow cytometric analysis by FITC (fluorescein isothiocyanate)- annexin V and propidium iodide showed that treatment with IC50 values of 8-GC and 8-GCC induced apoptosis in 35.2% and 30.8% of PC-3 cells, respectively. Conclusion: Thus, 8-GC and 8-GCC can be introduced as effective anticancer agents with apoptosis-inducing properties. Furthermore, our results suggest that the cytotoxic effects of these compounds might be related to the inhibition of 15-LOX-1 enzyme in PC-3 cells. On the other hand, the cytotoxic effects of 8-IC might be due to the inhibition of other signaling pathways in PC-3 cells. However, further in vivo experiments are required to determine the exact mechanisms involved in the anticancer effects of these coumarin compounds.
DOAJ (DOAJ: Directory of Open Access Journals), Mar 1, 2020
We have developed a rapid, quantitative method for analysing the outcome of the first strand synt... more We have developed a rapid, quantitative method for analysing the outcome of the first strand synthesis step in cDNA library preparation, yield and molecular weight range of the final cDNA products are determined after size fractionation. This method involves conventional cDNA library construction including all enzymatic steps usually required, but replaces radioactive labelling of nucleic acids with fluorescence detection. The separation and quantification steps all involve ion-pair reversed-phase high performance liquid chromatography (IP RP HPLC). This quantitative method replaces the use of autoradiography and size exclusion chromatography with combined ion-pair reversed-phase high performance liquid chromatography and in line fluorescence detection. The result of this approach is combination of speed with the generation of reproducible, high quality cDNA libraries.
Background & Aim Mesenchymal stem/stromal cells (MSCs) displayed potent immunosuppressive and... more Background & Aim Mesenchymal stem/stromal cells (MSCs) displayed potent immunosuppressive and anti-inflammatory properties, highlighting their potential application for treating inflammatory disorders. Being regulated by some pro-inflammatory cytokines, MSCs regulate nearly all immune cell populations. Previous studies showed that priming these cells with some agents could increase the paracrine effects of these cells to boost their therapeutic efficacy. Glibenclamide (Gly) causing hypoglycemia is broadly applicable in the type II diabetes mellitus. Besides, its protective role was shown in some inflammation-induced injuries. The anti-inflammatory effect of Gly is associated with reduced production of pro-inflammatory cytokines. This study aimed to investigate the effects of Gly on the immunomodulatory properties of MSCs. Methods, Results & Conclusion Human MSCs were isolated from the waste lipoaspirates (60 ml) obtained from healthy donors after informed consent, which was approved by the local ethics committee (IR.ACECR.JDM.REC.1396.7). The cytotoxicity of Gly on Adipose-derived MSCs (Ad-MSCs) was assessed through MTT (treatment with 50, 100, 200, and 500 μM of Gly for 24, 48, and 72 h). Ad-MSCs were treated with 500 μM of the Gly for 24 hours, the expression of pro-inflammatory cytokines including IL-1, IL-6, IL-8, MCP-1, and HGF, were evaluated via qPCR. The expression of an apoptotic related gene, caspase I, was also measured. Then, the impact of Gly on LPS -induced preventative effects were investigated through qPCR with the previous set of genes as well as TNF-α, following the induction of cells with LPS (5 Μg/ml for four h) and then treated with Gly for 24 h. The results of the MTT assay indicated that Gly in different concentrations, including 50, 100, 200, and 500 μM had no cytotoxicity effects on Ad-MSC. Priming these cells with Gly resulted in significantly decreased expression of some pro-inflammatory and also caspase genes (Fig. 1). Induction of Ad-MSCs with LPS led to increased expression of pro-inhibitory cytokines, and upon treatment of these cells with Gly, their pro-inflammatory effects were diminished (Fig. 2). These data suggest that pretreatment of MSCs with glibenclamide could enhance their immunomodulatory properties; hence it might be considered as a strategy to improve the efficiency of cellular therapy.
Introduction: Biological scaffolds materials derived from the extracellular matrix (ECM) have bee... more Introduction: Biological scaffolds materials derived from the extracellular matrix (ECM) have been created the most promising evolution in the field of tissue engineering. it seems that a clear understanding of such a matrix and attempt to make them applicable will let us to discover important ...
Breast cancer is the most common cancer in women worldwide. Traditional therapies are expensive a... more Breast cancer is the most common cancer in women worldwide. Traditional therapies are expensive and cause severe side effects. Targeted therapy is a powerful method to circumvent the problems of other therapies. It also allows drugs to localize at predefined targets in a selective manner. Currently, there are several monoclonal antibodies which target breast cancer cell surface markers. However, using antibodies has some limitations. In the last two decades, many investigators have discovered peptides that may be useful to target breast cancer cells. In this article, we provide an overview on anti-breast cancer peptides, their sources and biological activities. We further discuss the pros and cons of using anticancer peptides with further emphasis on how to improve their effectiveness in cancer therapy.
Anti-cancer Agents in Medicinal Chemistry, May 11, 2023
Introduction: Prostate cancer is the second most prevalent cancer among men. Despite different tr... more Introduction: Prostate cancer is the second most prevalent cancer among men. Despite different treatments, including surgery, chemotherapy, radiation therapy, hormone therapy and immunotherapy for this disease, patients ultimately progress to advanced states. Thus, there is a need for new treatment options targeting cell growth and apoptosis to better control the proliferation and metastasis of these cells. There are many reports indicating overexpression of the 15-lipoxygenase-1 (15-LOX-1) enzyme in prostate tumors. Studies have also shown that inhibition of this enzyme prevents the progression of prostate cancer. Objective: This study was conducted to assess the anti-cancer properties of some coumarin derivatives as possible 15- LOX-1 inhibitors, on PC-3 prostate cancer cells. Methods: In this study, the activity of 15-LOX-1 was evaluated in PC-3 cells by a spectrophotometric assay. In addition, due to high similarity between the 15-LOX-1 and soybean 15-lipoxygenase (SLO) (L1; EC 1, 13, 11, 12) active sites, the soybean SLO was used to investigate inhibitory effects of synthetic coumarin compounds 8- isopentenyloxycoumarin (8-IC), 8-isopentenyloxy-3-carboxycoumarin (8-ICC), 8-geranyloxycoumarin (8-GC), 8- geranyloxy-3-carboxycoumarin (8-GCC), and 8-farnesyloxy-3-carboxycoumarin (8-FCC) on this enzyme. Moreover, the cytotoxic and anticancer effects of the coumarin compounds were examined on PC-3 (Prostate Cancer) and HDF-1 (Human Dermal Fibroblast) cells by assay. Finally, apoptosis-inducing effects of alamarBlue all synthetic compounds were determined by flow cytometry. Results: The IC50 values obtained by the alamarBlue test revealed that 8-IC, 8-GC and 8-GCC had cytotoxic effects on PC-3 cells. Treating both PC-3 and HDF-1 cells with 8-ICC and 8-FCC did not significantly reduce cell number. Furthermore, the IC50 values of 8-IC on HDF-1 cells showed cytotoxic effects, while treating these cells with 8-GC and 8- GCC did not show any significant cytotoxicity on these normal human fibroblasts. Assessing the ability of 4-MMPB (as a specific inhibitor of 15-LOX-1), 8-GC, and 8-GCC compounds to inhibit SLO revealed that these compounds exerted strong 15-LOX-1 inhibitory activity, while 8-IC and 8-FCC had a weak inhibitory effect and also 8-ICC showed no inhibitory effect on SLO enzyme. In addition, flow cytometric analysis by FITC (fluorescein isothiocyanate)- annexin V and propidium iodide showed that treatment with IC50 values of 8-GC and 8-GCC induced apoptosis in 35.2% and 30.8% of PC-3 cells, respectively. Conclusion: Thus, 8-GC and 8-GCC can be introduced as effective anticancer agents with apoptosis-inducing properties. Furthermore, our results suggest that the cytotoxic effects of these compounds might be related to the inhibition of 15-LOX-1 enzyme in PC-3 cells. On the other hand, the cytotoxic effects of 8-IC might be due to the inhibition of other signaling pathways in PC-3 cells. However, further in vivo experiments are required to determine the exact mechanisms involved in the anticancer effects of these coumarin compounds.
DOAJ (DOAJ: Directory of Open Access Journals), Mar 1, 2020
We have developed a rapid, quantitative method for analysing the outcome of the first strand synt... more We have developed a rapid, quantitative method for analysing the outcome of the first strand synthesis step in cDNA library preparation, yield and molecular weight range of the final cDNA products are determined after size fractionation. This method involves conventional cDNA library construction including all enzymatic steps usually required, but replaces radioactive labelling of nucleic acids with fluorescence detection. The separation and quantification steps all involve ion-pair reversed-phase high performance liquid chromatography (IP RP HPLC). This quantitative method replaces the use of autoradiography and size exclusion chromatography with combined ion-pair reversed-phase high performance liquid chromatography and in line fluorescence detection. The result of this approach is combination of speed with the generation of reproducible, high quality cDNA libraries.
Background & Aim Mesenchymal stem/stromal cells (MSCs) displayed potent immunosuppressive and... more Background & Aim Mesenchymal stem/stromal cells (MSCs) displayed potent immunosuppressive and anti-inflammatory properties, highlighting their potential application for treating inflammatory disorders. Being regulated by some pro-inflammatory cytokines, MSCs regulate nearly all immune cell populations. Previous studies showed that priming these cells with some agents could increase the paracrine effects of these cells to boost their therapeutic efficacy. Glibenclamide (Gly) causing hypoglycemia is broadly applicable in the type II diabetes mellitus. Besides, its protective role was shown in some inflammation-induced injuries. The anti-inflammatory effect of Gly is associated with reduced production of pro-inflammatory cytokines. This study aimed to investigate the effects of Gly on the immunomodulatory properties of MSCs. Methods, Results & Conclusion Human MSCs were isolated from the waste lipoaspirates (60 ml) obtained from healthy donors after informed consent, which was approved by the local ethics committee (IR.ACECR.JDM.REC.1396.7). The cytotoxicity of Gly on Adipose-derived MSCs (Ad-MSCs) was assessed through MTT (treatment with 50, 100, 200, and 500 μM of Gly for 24, 48, and 72 h). Ad-MSCs were treated with 500 μM of the Gly for 24 hours, the expression of pro-inflammatory cytokines including IL-1, IL-6, IL-8, MCP-1, and HGF, were evaluated via qPCR. The expression of an apoptotic related gene, caspase I, was also measured. Then, the impact of Gly on LPS -induced preventative effects were investigated through qPCR with the previous set of genes as well as TNF-α, following the induction of cells with LPS (5 Μg/ml for four h) and then treated with Gly for 24 h. The results of the MTT assay indicated that Gly in different concentrations, including 50, 100, 200, and 500 μM had no cytotoxicity effects on Ad-MSC. Priming these cells with Gly resulted in significantly decreased expression of some pro-inflammatory and also caspase genes (Fig. 1). Induction of Ad-MSCs with LPS led to increased expression of pro-inhibitory cytokines, and upon treatment of these cells with Gly, their pro-inflammatory effects were diminished (Fig. 2). These data suggest that pretreatment of MSCs with glibenclamide could enhance their immunomodulatory properties; hence it might be considered as a strategy to improve the efficiency of cellular therapy.
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