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Silver Nanoparticles Exert Apoptotic Activity in Bladder Cancer 5637 Cells Through Alteration of Bax/Bcl-2 Genes
Sajedeh Daei1, Nasrin Ziamajidi1,2, Roghayeh Abbasalipourkabir1
1Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Abstract:
Bladder cancer is defined as a urinary tract malignancy that threatens men's and women's health. Due to the side effects of common chemotherapies, novel therapeutic strategies are necessary to overcome the issues concerning bladder cancer treatments. Nanotechnology has been suggested as a means to develop the next-generation objectives of cancer diagnosis and treatment among various novel therapies. Owing to the special characteristics that they can offer, silver nanoparticles (AgNPs) were investigated in this study to evaluate their apoptotic impact on bladder cancer 5637 cells. In this study, an MTT assay was conducted and appropriate concentrations of AgNPs were selected. Moreover, reactive oxygen species (ROS) production and apoptosis levels were determined using fluorimetric and Annexin/PI flow cytometry assays, respectively. Moreover, the activity of caspase 3,7, mRNA expression of Bax (Bcl-2-associated X) and Bcl-2 (B-cell lymphoma 2) were assessed based on colorimetric and qRT-PCR methods, respectively. The results indicated that AgNPs can significantly reduce the viability of 5637 cells in a dose-dependent mode as well as having the ability to elevate ROS production. Flow cytometry data showed that AgNPs lead to a remarkable increase in the apoptosis rate as compared with the control. Consistent with this, the induction of apoptosis was revealed by the overexpression of Bax, accompanied by a reduction in Bcl-2 expression compared to the control. Furthermore, AgNPs remarkably stimulated caspase 3,7 activation. In summary, AgNPs can mediate apoptosis in 5637 cells via excessive ROS formation, up-regulating Bax/Bcl-2 expression, and caspase 3,7 activation.
Insights
Silver nanoparticles (AgNPs) show promise for treating bladder cancer by inducing cell death. These nanoparticles reduce cancer cell viability and trigger apoptosis through increased ROS and caspase activation.
Area of Science:
- Oncology
- Nanotechnology
- Biochemistry
Background:
- Bladder cancer poses a significant health threat, necessitating novel therapeutic strategies beyond conventional chemotherapy.
- Nanotechnology offers innovative approaches for cancer diagnosis and treatment.
- Silver nanoparticles (AgNPs) possess unique properties making them candidates for cancer therapy.
Purpose of the Study:
- To investigate the apoptotic effects of silver nanoparticles (AgNPs) on bladder cancer 5637 cells.
- To evaluate AgNPs' potential as a novel therapeutic agent for bladder cancer.
Main Methods:
- MTT assay to determine optimal AgNP concentrations and assess cell viability.
- Fluorimetric and Annexin/PI flow cytometry assays to measure reactive oxygen species (ROS) production and apoptosis levels.
- Colorimetric and qRT-PCR methods to assess caspase 3,7 activity and mRNA expression of Bax and Bcl-2.
Main Results:
- AgNPs significantly reduced 5637 bladder cancer cell viability in a dose-dependent manner.
- AgNPs elevated ROS production and increased apoptosis rates in cancer cells.
- AgNPs upregulated Bax expression, downregulated Bcl-2 expression, and activated caspase 3,7, confirming apoptosis induction.
Conclusions:
- Silver nanoparticles effectively mediate apoptosis in bladder cancer 5637 cells.
- The mechanism involves excessive ROS formation, modulation of Bax/Bcl-2 expression, and caspase 3,7 activation.
- AgNPs represent a potential nanotherapeutic strategy for bladder cancer treatment.
