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Antioxidant potential of ganoderic acid in Notch-1 protein in neuroblastoma

  • Balraj Singh Gill
  • Navgeet
  • Sanjeev Kumar
Article
  • 65 Downloads

Abstract

Neuroblastoma is a childhood tumor arising from developing a sympathetic nervous system and causes around 10% of pediatric tumors. Despite advancement in the use of sophisticated techniques in molecular biology, neuroblastoma patient’s survivability rate is very less. Notch pathway is significant in upholding cell maintenance and developmental process of organs. Notch-1 proteins are a ligand-activated transmembrane receptor which decides the fate of the cell. Notch signaling leads to transcription of genes which indulged in numerous diseases including tumor progression. Ganoderic acid, a lanosterol triterpene, isolated from fungus Ganoderma lucidum with a wide range of medicinal values. In the present study, various isoforms of the ganoderic acid and natural inhibitors were docked by molecular docking using Maestro 9 in the Notch-1 signaling pathway. The receptor-based molecular docking exposed the best binding interaction of Notch-1 with ganoderic acid A with GScore (− 8.088), kcal/mol, Lipophilic EvdW (− 1.74), Electro (− 1.18), Glide emodel (− 89.944) with the active participation of Arg 189, Arg 199, Glu 232 residues. On the other hand natural inhibitor, curcumin has GScore (− 7.644), kcal/mol, Lipophilic EvdW (− 2.19), Electro (− 0.73), Glide emodel (− 70.957) with Arg 75 residues involved in docking. The ligand binding affinity of ganoderic acid A in Notch-1 is calculated using MM-GBSA (− 76.782), whereas curcumin has (− 72.815) kcal/mol. The QikProp analyzed the various drug-likeness parameters such as absorption, distribution, metabolism, excretion, and toxicity (ADME/T) and isoforms of ganoderic acid require some modification to fall under Lipinski rule. The ganoderic acid A and curcumin were the best-docked among different compounds and exhibits downregulation in Notch-1 mRNA expression and inhibits proliferation, viability, and ROS activity in IMR-32 cells.

Keywords

Notch-1 Cancer Ganoderic acid ROS Antioxidant 

Abbreviations

ROS

Reactive oxygen species

DMEM

Dulbecco’s modified Eagle’s medium

FBS

Fetal bovine serum

PBS

Phosphate-buffered saline

PCR

Polymerase chain reaction

Notes

Acknowledgements

The authors thank Central University of Punjab, Bathinda, for providing the necessary facilities to carry out the present work.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Centre for BiosciencesCentral University of PunjabBathindaIndia
  2. 2.Department of Higher EducationShimlaIndia
  3. 3.Department of BiotechnologyKMV CollegeJalandharIndia
  4. 4.Centre for Plant SciencesCentral University of PunjabBathindaIndia

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