ChemInform Abstract: Synthesis and Anticancer Effects of Some Novel Pyrazolo[3,4-d]pyrimidine Derivatives by Generating Reactive Oxygen Species in Human Breast Adenocarcinoma Cells.

Manganese (Mn) complexes are widely studied because of their important catalytic properties in synthetic and biochemical reactions. A Mn (III) complex of an amidoamine ligand was synthesized using a tetradentate amidoamine ligand. In this study, the Mn (III) complex was evaluated for its biological activity by measuring its cytotoxicity in human breast adenocarcinoma cell line (MCF-7). Cytotoxic effects of the Mn (III) complex were determined using established biomarkers in an attempt to delineate the mechanism of action and the utility of the complex as a potential anticancer drug. The Mn (III) complex induces cell death in a dose- and time-dependent manner as shown by microculture tetrazolium assay, a measure of cytotoxic cell death. Our results demonstrated that cytotoxic effects were significantly increased at higher concentrations of Mn (III) complex and with longer time of treatment. The IC50 (Inhibitor concentration that results in 50% cell death) value of Mn (III) complex in MCF-7 cells was determined to be 2.5 mmol/L for 24 hours of treatment. In additional experiments, we determined the Mn (III) complex–mediated cell death was due to both apoptotic and nonspecific necrotic cell death mechanisms. This was assessed by ethidium bromide/acridine orange staining and flow cytometry techniques. The Mn (III) complex produced reactive oxygen species (ROS) triggering the expression of manganese superoxide dismutase 1 and ultimately damaging the mitochondrial function as is evident by a decline in mitochondrial membrane potential. Treatment of the cells with free radical scavenger, N, N-dimethylthiourea decreased Mn (III) complex–mediated generation of ROS and attenuated apoptosis. Together, these results suggest that the Mn (III) complex–mediated MCF-7 cell death utilizes combined mechanism involving apoptosis and necrosis perhaps due to the generation of ROS.

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Two Novel Curcumin Analogues Induced Reactive Oxygen Species Generation and Mitochondrial-Related Apoptosis in Human Breast Cancer MCF - 7 Cells

Journal of Applied Pharmacy ◽

10.4172/1920-4159.1000215 ◽

2016 ◽

Vol 08 (02) ◽

Author(s):

Shuyue Luo ◽

Qingyong Li

Keyword(s):

Breast Cancer ◽

Reactive Oxygen Species ◽

Human Breast Cancer ◽

Reactive Oxygen Species Generation ◽

Reactive Oxygen ◽

Oxygen Species ◽

Human Breast ◽

Curcumin Analogues ◽

Mcf 7

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Change in the Expression of BAK، FAS، BAX، TNF-A، BCL-2 and Survivin Apoptosis Genes of the Human Breast Adenocarcinoma Cells (MCF-7) by Staphylococcal Enterotoxin B

Journal of Shahid Sadoughi University of Medical Sciences ◽

10.18502/ssu.v27i6.1602 ◽

2019 ◽

Author(s):

Sara Afzali ◽

Abbas Doosti ◽

Mansour Heidari ◽

Nahid Babaei ◽

Parvaneh Keshavarz

Keyword(s):

Staphylococcal Enterotoxin ◽

Breast Adenocarcinoma ◽

Control Group ◽

Staphylococcal Enterotoxin B ◽

Type B ◽

Human Breast ◽

Human Breast Adenocarcinoma ◽

Adenocarcinoma Cells ◽

Enterotoxin B ◽

Mcf 7

Introduction: Breast cancer is one of the most prevalent malignancies among women. Patients whose suffering from this condition, as a result of the use of conventional therapies often have a poor response to treatment and the relapse among them is frequent. In this study, the effects of staphylococcal enterotoxin type B on BAK، FAS، BAX، TNF-a، BCL-2 و Survivin genes expression in human breast adenocarcinoma cells (MCF-7) was examined. Staphylococcal enterotoxin B is a powerful member of the Staphylococcus aureus toxins family, which is known as an anticancer agent with potential for killing cancer cells. Methods: The experimental study was carried out at the Biotechnology Research Center of Islamic Azad University, Shahrekord Branch. By using Lipofectamine 2000 reagent, MCF-7 cells transfected with the pcDNA3.1(+)-seb (recombinant) and pcDNA3.1(+) (non-recombinant) plasmids and were selected by culturing in a selective medium of RPMI- 1640 containing 600 μg / mL antibiotic G418. Then, the expression of BAK, FAS, BAX, TNF-a, BCL-2, and Survivin genes in transfected cells were analyzed by real time PCR. Student's t-test, SPSS Inc., Chicago, IL; Version 16 and also Excel program for statistical analysis were used. Results: The results of this study indicated that staphylococcal enterotoxin type B (SEB) remarkably changes the expression of apoptotic related genes in MCF-7 cell line. It was observed a significant increase in the expression of BAK, FAS, BAX, and TNF-a genes, the expression of BCL-2 and Survivin genes significantly decreased compared to the control group (P=0/032). Conclusion: Staphylococcal enterotoxin type B has an inhibitory effect on the growth, proliferation and invasion of breast adenocarcinoma cells through altering the expression of the genes involved in the apoptosis process. Therefore, it seems that there is a good research field for the use of this toxin in the control and treatment of human breast adenocarcinoma.

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