Targeting Cell Cycle Checkpoints and Apoptotic Resistance in Lung Adenocarcinoma: An In Silico Approach to Natural Compound Therapeutics
Keywords:
Lung adenocarcinoma, Chk1, PARP1, apigenin, molecular docking, ADMETAbstract
Lung cancer remains a challenging because of its aggressive nature and limited treatment options. This study investigates the clinical significance of Chk1 and PARP1 overexpression in lung cancer and evaluated the potential natural compound as potential inhibitor. Bioinformatics analysis of TCGA data revealed significant upregulation of Chk1 and PARP1 in LUAD tissues compared to normal controls (p<0.05), high expression was found to be significantly correlated with poor overall survival. ADMET profiling was done to evaluate the pharmacological properties the compounds. Apigenin exhibited no Lipinski rule violations and was therefore selected for further studies. Molecular docking demonstrated strong binding of apigenin to both targets, with binding energies of -9.7 kcal/mol and -8.6 kcal/mol with Chk1 and PARP1 respectively, suggesting competitive inhibition at the ATP-binding and catalytic domains respectively. These computational findings align with existing experimental evidence of the ability of apigenin to induce G2/M arrest and sensitize cancer cells to DNA-damaging agents. This study proposes a novel therapeutic strategy combining apigenin with PARP inhibitors to obtain better patient outcomes in lung cancer cases by potentially overcoming chemoresistance. The findings of this study can further be validated by in vitro/ in vivo experiments to assess the efficacy of apigenin in modulating the Chk1/PARP1 pathways and improving treatment outcomes in lung cancer.
How to cite this article:
Rahman F, Ali S M, Dev K. Targeting Cell Cycle
Checkpoints and Apoptotic Resistance in Lung
Adenocarcinoma: An In Silico Approach to Natural
Compound Therapeutics. Rec Adv Path Lab Med.
2025;11(1&2):1-6.
DOI: https://doi.org/10.24321/2454.8642.202502
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