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Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection
Published on: October 25, 2013
Investigating Anti-Breast Cancer Properties of the Antibiotic Vancomycin-A Drug Repurposing study using In Silico
Narendra Banerjee1, Jazmine Cuffee1, Brent Lake1
1Department Of Natural And Pharmaceutical Sciences. Elizabeth City State University Campus Of The University Of North Carolina. Elizabeth City, North Carolina- 27909, USA.
Abstract:
The incidence of triple-negative breast cancer (TNBC) is approximately 10-15% of all breast cancer cases around the world. It is important to search for novel therapeutic agents against TNBC since this form of cancer is a leading cause of death in women worldwide. Various genetic mutations in TNBC patients have been identified. EZH2 is an oncoprotein involved in breast, prostate, colon, and other cancers. In silico drug design and bioinformatics studies helped to identify the FDA approved antibiotic, vancomycin as a potential inhibitor of the EZH2 oncoprotein. A drug repurposing study of vancomycin to investigate the potential anti TNBC properties was tested by doing cytotoxicity analysis with vancomycin in TNBC cell lines by WST-8 assay, spheroid forming assay and ROS generation experiments. The EZH2 inhibitor property of vancomycin was studied by RT-PCR and ELISA assay. Our initial results showed that Vancomycin effectively prevents cell proliferation, spheroid formation and generates ROS in the TNBC cell lines tested as well as inhibit the EZH2 gene expression.
Insights
Vancomycin, an antibiotic, shows promise in treating triple-negative breast cancer (TNBC) by inhibiting the EZH2 oncoprotein. This study explored vancomycin
Area of Science:
- Oncology
- Pharmacology
- Bioinformatics
Background:
- Triple-negative breast cancer (TNBC) accounts for 10-15% of breast cancer cases globally and is a significant cause of cancer-related mortality in women.
- The EZH2 oncoprotein is implicated in the progression of various cancers, including breast cancer.
- Identifying novel therapeutic strategies and drug repurposing candidates for TNBC is crucial due to limited treatment options.
Purpose of the Study:
- To investigate the potential anti-TNBC properties of vancomycin through drug repurposing.
- To evaluate vancomycin's efficacy in inhibiting the EZH2 oncoprotein.
- To assess vancomycin's impact on TNBC cell proliferation, spheroid formation, and reactive oxygen species (ROS) generation.
Main Methods:
- In silico drug design and bioinformatics approaches were used to identify potential drug candidates.
- Vancomycin's cytotoxicity in TNBC cell lines was assessed using WST-8 assays.
- Spheroid formation assays, ROS generation experiments, RT-PCR, and ELISA were employed to evaluate vancomycin's effects on TNBC cells and EZH2 expression.
Main Results:
- Vancomycin demonstrated significant inhibition of TNBC cell proliferation and spheroid formation.
- Treatment with vancomycin led to increased ROS generation in TNBC cell lines.
- Vancomycin effectively inhibited EZH2 gene expression in the tested TNBC cell lines.
Conclusions:
- Vancomycin exhibits potential as a therapeutic agent against triple-negative breast cancer.
- The anti-cancer effects of vancomycin in TNBC are associated with the inhibition of EZH2.
- This study supports the repurposing of vancomycin for TNBC treatment, warranting further investigation.
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