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Alhagi maurorum Extract Regulates the PI3K/AKT Cascade and Inhibits the Proliferation of the Lung Cancer Cell Line
Fereshteh Ramezani Zardanjani1, Hajar Yaghoobi2, Abbas Alibakhshi3
1Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Background:
This study investigates the anticancer effects of hydroalcoholic Alhagi maurorum extract on non-small-cell lung cancer.
Materials And Methods:
Signaling pathways in non-small-cell lung cancer were analyzed using the EnrichR website and KEGG algorithms associated with the GSE50627 dataset. The protein-protein interaction network was analyzed using STRING software. The compounds in A. maurorum extract were obtained from the PubChem database. The proteins involved in the signaling pathways were docked with the compounds in A. maurorum extract using AutoDock software. Finally, a molecular dynamics simulation was performed using GROMACS 5.1.1 software. DPPH and MTT assays were used to determine the antioxidant and cytotoxic effects of the extract on A549 lung cancer cells, respectively. The gene expression related to KEGG pathways was evaluated by real-time PCR.
Results:
The PI3K-Akt signaling was the most prevalent pathway in GSE50627, associated with non-small-cell lung cancer. Results showed the inhibitory potential of A. maurorum on A549 cells, with an IC50 of 277 μg/ml. The extract inhibited free radicals at increasing concentrations. A. maurorum extract inhibited PTEN as a specific target in the PI3K/AKT signaling pathway.
Conclusion:
Therefore, the hydroalcoholic extract of A. maurorum may be a suitable candidate for inhibiting the PI3K/AKT signaling pathway in lung cancer.
Insights
Alhagi maurorum extract shows anticancer effects against non-small-cell lung cancer. This natural compound inhibits the PI3K/AKT pathway, offering potential for lung cancer treatment.
Area of Science:
- Phytochemistry
- Molecular Biology
- Oncology
Background:
- Non-small-cell lung cancer (NSCLC) remains a significant health concern.
- Investigating natural compounds for anticancer properties is crucial for novel therapeutic development.
Purpose of the Study:
- To evaluate the anticancer effects of hydroalcoholic *Alhagi maurorum* extract on NSCLC.
- To identify the molecular targets and pathways affected by *A. maurorum* in lung cancer cells.
Main Methods:
- Bioinformatic analysis of NSCLC signaling pathways (KEGG, EnrichR, STRING).
- Molecular docking and dynamics simulations of *A. maurorum* compounds against pathway targets.
- In vitro antioxidant (DPPH) and cytotoxic (MTT) assays on A549 lung cancer cells.
- Real-time PCR for gene expression analysis related to KEGG pathways.
Main Results:
- The PI3K-Akt signaling pathway was identified as a key pathway in NSCLC.
- *A. maurorum* extract demonstrated cytotoxic effects on A549 cells with an IC50 of 277 μg/ml.
- The extract exhibited antioxidant activity and specifically inhibited PTEN within the PI3K/AKT pathway.
Conclusions:
- Hydroalcoholic *Alhagi maurorum* extract possesses anticancer properties against NSCLC.
- The extract's mechanism involves the inhibition of the PI3K/AKT signaling pathway, potentially by targeting PTEN.
- *A. maurorum* is a promising candidate for developing novel lung cancer therapeutics.
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