In-silico and in-vitro study reveals ziprasidone as a potential aromatase inhibitor against breast carcinoma.

Aromatase enzyme plays a fundamental role in the development of estrogen receptors, and due to this functionality, the enzyme has gained significant attention as a therapeutic for reproductive disorders and cancer diseases. The currently employed aromatase inhibitors have severe side effects whereas our novel aromatase inhibitor is more selective and less toxic, therefore has greater potential to be developed as a drug. The research framework of this study is to identify a potent inhibitor for the aromatase target by profiling molecular descriptors of the ligand and to find a functional pocket in the target by docking and MD simulations. For assessing cellular and metabolic activities as indicators of cell viability and cytotoxicity, in-vitro studies were performed by using the colorimetric MTT assay. Aromatase activities were determined by a fluorometric method. Cell morphology was assessed by phase-contrast light microscopy. Flow cytometry and Annexin V-FITC/PI staining assay determined cell cycle distribution and apoptosis. This study reports that CHEMBL708 (Ziprasidone) is the most promising compound that showed excellent aromatase inhibitory activity. By using better drug design methods and experimental studies, our study identified a novel compound that could be effective as a high-potential drug candidate against aromatase enzyme. We conclude that the compound ziprasidone effectively blocks the cell cycle at the G1-S phase and induces cancer cell death. Further, in-vivo studies are vital for developing ziprasidone as an anticancer agent. Lastly, our research outcomes based on the results of the in-silico experiments may pave the way for identifying effective drug candidates for therapeutic use in breast cancer.

Proteoglycans in breast cancer, identification and characterization by LC-MS/MS assisted proteomics approach: A review.

PURPOSE: Proteoglycans (PGs) are negatively charged macromolecules containing a core protein and single or several glycosaminoglycan chains attached by covalent bond. They are distributed in all tissues, including extracellular matrix (ECM), cell surface, and basement membrane. They are involved in major pathways and cell signalling cascades which modulate several vital physiological functions of the body. They have also emerged as a target molecule for cancer treatment and as possible biomarkers for early cancer detection. Among cancers, breast cancer is a highly invasive and heterogenous type and has become the major cause of mortality especially among women. So, this review revisits the studies on PGs characterization in breast cancer using LC-MS/MS-based proteomics approach, which will be further helpful for identification of potential PGs-based biomarkers or therapeutic targets. EXPERIMENTAL DESIGN: There is a lack of comprehensive knowledge on the use of LC-MS/MS-based proteomics approaches to identify and characterize PGs in breast cancer. RESULTS: LC-MS/MS assisted PGs characterization in breast cancer revealed the vital PGs in breast cancer invasion and progression. In addition, comprehensive profiling and characterization of PGs in breast cancer are efficiently carried out by this approach. CONCLUSIONS: Proteomics techniques including LC-MS/MS-based identification of proteoglycans is effectively carried out in breast cancer research. Identification of expression at different stages of breast cancer is a major challenge, and LC-MS/MS-based profiling of PGs can boost novel strategies to treat breast cancer, which involve targeting PGs, and also aid early diagnosis using PGs as biomarkers.