Pharmacological Study of A3 Adenosine Receptor agonist (AB Meca) in Xenograft Lung Cancer Model in Mice through In Silico and In Vivo Approach: Targeting TNF-α

(E-pub Ahead of Print)

Author(s): Nilay Solanki*, Leena Patel, Shaini Shah, Ashish Patel, Swayamprakash Patel, Mehul Patel, Umang Shah

Journal Name: Current Drug Discovery Technologies


Article ID: e100821195498
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Abstract:

Background: Lung cancer is the leading cause of mortality in India. Adenosine Receptor (AR) has emerged as a novel cancer-specific target. A3AR levels are upregulated in various tumor cells, which may mean that the specific AR may act as a biological marker and target specific ligands leading to cell growth inhibition.

Aim: Our aim was to study the efficacy of the adenosine receptor agonist, AB MECA, by in silico (molecular docking) and in vitro (human cancer cells in xenografted mice) studies.

Methods: Molecular docking on the AB-meca and TNF-α was performed using AutoDock. A549 Human lung cancer 2 ×106 cells per microliter per mouse injected via intrabronchial route. Rat TNF-α level was assessed by ELISA method.

Results: AB Meca's predicted binding energy (beng) with TNF-α was 97.13 kcal/mol, and the compatible docking result of a small molecular inhibitor with TNF-α native ligand beng was 85.76 kcal/mol. In vivo, a single dose of lung cancer cell A549 is being researched to potentiate tumor development. Doxorubicin and A3AR agonist therapies have lowered TNF-alpha levels that were associated with in silico function. The A3AR Agonist showed myeloprotective effects in the groups treated along with doxorubicin.

Conclusion: AB MECA’s higher binding energy (beng) with TNF-α mediated reduction of tumor growth in our lung cancer in vivo model suggested that it may be an effective therapy for lung cancer.

Keywords: Molecular docking, lung cancer, A3 adenosine receptor agonist, TNF- α, doxorubicin, adenosine receptor.

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Article Details

Article ID: e100821195498
(E-pub Ahead of Print)
DOI: 10.2174/1570163818666210810142022
Price: $95