In silico and in vitro investigation of dual targeting Prima-1^MET as precision therapeutic against lungs cancer

Abstract

This study emphasizes the explorations of binding of Prima-1^MET with two targets, p53 a tumor suppressor protein, and tyrosine kinase of epidermal growth factor receptor. In silico investigations reveal that Prima-1^MET showed robust binding with both targets. Molecular docking simulations demonstrated the binding affinity of Prima-1^MET with p53 and tyrosine kinase was found to be −38.601 kJ/mol and −38.976 kJ/mol. In addition, the stability of Prima-1^MET was explored by molecular dynamics simulation. Prima-1^MET attains stability in the binding site of the respective protein till the simulation period is over. Moreover, the free binding energy ΔG_bind was calculated by the molecular mechanics Poisson Boltzmann surface area method. The ΔG_bind of Prima-1^MET with tyrosine kinase was found to be −58.585 ± 0.327 kJ/mol and with p53 it was −35.910 ± 0.335 kJ/mol. Next, cytotoxicity of the Prima-1^MET was evaluated using multiple cancer cell lines and the IC₅₀ value were ranging between 4.5 and 30 μM. The cell death was identified by apoptosis assay. Further, the p53 and tyrosine kinase expression was monitored using immunofluorescence techniques, it was found Prima-1^MET induces the expression of p53 protein and mimics the level of tyrosine kinase oncogenic target. Also, reactive oxygen species (ROS) and membrane potential activity of Prima-1^MET was evaluated by using a lung cancer cell line. A significant decrease in intracellular ROS was observed and resulted in disruption of mitochondrial transmembrane potential. This study uncovers the underlying mechanism of Prima-1^MET and could be helpful to design further leads against lung cancers.

Communicated by Ramaswamy H. Sarma

Keywords:

• Prima-1^MET
• lungs cancer
• cytotoxicity
• p53
• EGFR
• apoptosis
• ROS
• MTP

Disclosure statement

All authors have no conflict of interest and all data will be available on the authors’ request.

Authors’ contributions

RKM and SAM contributes to in silico, in vitro work and Draft preparations. SSA contributes to in vitro study, and editing. All author read and approve the final manuscript for publication.

Acknowledgments

All authors are thankful to Dr. Binata Nayak, Professor, School of Life Sciences, Sambalpur University for critical revisions, editing, constructive suggestions and provide laboratory facilities to conduct the present study. SAM wishes to acknowledge Dr. Ibrahim Khalifa, Behna University, Egypt for providing access to MOE tools.

Additional information

Funding

There is no funding’s associated with the research.