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Utilization of the Soft Agar Colony Formation Assay to Identify Inhibitors of Tumorigenicity in Breast Cancer Cells
Published on: May 20, 2015
Network-Derived Radioresistant Breast Cancer Target with Candidate Inhibitors from Brown Algae: A Sequential
Mahema Sivakumar1, Sheikh F Ahmad2, Talha Bin Emran3,4
1Drug Discovery and Multi-Omics Laboratory, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education, Chettinad Hospital and Research Institute, Kelambakkam 603103, Tamil Nadu, India.
Abstract:
Despite significant progress in early detection and treatment, a few aggressive breast cancers still exhibit resistance to therapy. This study aimed to identify a therapeutic target for radioresistant breast cancer (RRbc) through a protein network from breast cancer genes and to evaluate potent phytochemicals against the identified target. Our approach includes the integration of differential expression genes from expression datasets to create a protein network and to use survival analysis to identify the crucial RRbc protein in order to discover a therapeutic target. Next, the phytochemicals sourced from brown algae were screened through molecular docking, ADME (absorption, distribution, metabolism, and excretion), molecular dynamics (MD) simulation, MM-GBSA, and quantum mechanics against the identified target. As a result of our protein network investigation, the proto-oncogene c-KIT (KIT) protein was identified as a potent radioresistant breast cancer target. Further, phytochemical screening establishes that nahocol-A1 from brown algae has high binding characteristics (-8.56 kcal/mol) against the KIT protein. Then, quantum chemical analysis of nahocol-A1 provided insights into its electronic properties favorable for protein binding. Also, MD simulation comprehends the conformational stability of the KIT-nahocol-A1 complex. Overall, our findings suggest nahocol-A1 could serve as a promising therapeutic candidate for radioresistant breast cancer.
Insights
Researchers identified the proto-oncogene c-KIT (KIT) as a target for radioresistant breast cancer (RRbc). Nahocol-A1, a phytochemical from brown algae, shows promise as a therapeutic candidate, demonstrating strong binding to the KIT protein.
Area of Science:
- Oncology
- Biochemistry
- Pharmacology
Background:
- Aggressive breast cancers can develop resistance to therapy, necessitating novel treatment strategies.
- Identifying specific molecular targets is crucial for developing effective therapies for radioresistant breast cancer (RRbc).
Purpose of the Study:
- To identify a novel therapeutic target for radioresistant breast cancer (RRbc) by analyzing protein networks.
- To evaluate phytochemicals from brown algae as potential therapeutic agents against the identified target.
Main Methods:
- Integrated differential gene expression data to construct a protein-protein interaction network.
- Performed survival analysis to pinpoint a critical RRbc protein target.
- Screened brown algae-derived phytochemicals using molecular docking, ADME, molecular dynamics (MD) simulation, MM-GBSA, and quantum mechanics.
Main Results:
- The proto-oncogene c-KIT (KIT) was identified as a key therapeutic target for RRbc.
- Nahocol-A1 from brown algae exhibited strong binding affinity (-8.56 kcal/mol) to the KIT protein.
- Quantum chemical analysis and MD simulations confirmed nahocol-A1's favorable electronic properties and conformational stability with KIT.
Conclusions:
- Nahocol-A1 demonstrates significant potential as a therapeutic candidate for radioresistant breast cancer.
- Targeting the KIT protein with nahocol-A1 offers a promising strategy for overcoming radioresistance in breast cancer.
