Investigating the Therapeutic Effects of Naringenin and Oleuropein on Prostate Cancer Cell Mat-LyLu via miR-155-5p: A Bioinformatics and Molecular Docking Analysis of KRAS and CDK2 Networks

TL;DR

This study explores how naringenin and oleuropein, found in citrus and olive products, may help treat prostate cancer by boosting miR-155-5p and targeting key cancer-related proteins.

Contribution

The study introduces a novel combination of bioinformatics and molecular docking to explore the therapeutic potential of naringenin and oleuropein in prostate cancer.

Findings

Naringenin and oleuropein significantly increase miR-155-5p expression in prostate cancer cells.

Molecular docking shows naringenin binds to KRAS and oleuropein to CDK2, inhibiting oncogenic pathways.

Both compounds show favorable pharmacokinetic profiles, suggesting potential for oral administration.

Abstract

Background: This study systematically investigates the therapeutic effects of naringenin (NAR) and oleuropein (OLE) on prostate cancer through miR-155-5p regulation. Methods: Experimental studies conducted on MAT-LyLu prostate cancer cell lines revealed that the application of NAR (50 μM) and OLE (75 μM) significantly increased miR-155-5p expression by 2.89-fold and 1.74-fold, respectively (p < 0.05). Bioinformatics analyses have indicated that miR-155-5p interacts with critical oncogenic pathways such as KRAS, CDK2, NF-κB, and TGF-β/Smad2. Computational analyses have revealed that miR-155-5p interacts with 16 critical oncogenic targets, including KRAS and CDK2. Molecular docking studies showed that NAR binds to the Switch I/II region of KRAS with a binding energy of −8.2 kcal/mol, while OLE binds to the ATP-binding pocket of CDK2 with an affinity of −9.1 kcal/mol. Pharmacokinetic evaluations revealed that NAR indicated high oral bioavailability (93.763% HIA) and full compliance with Lipinski’s rules, while OLE required advanced formulation strategies due to its high polarity. Network pharmacology analyses have shown that NAR affects lysosomal functions and enzyme regulation, while OLE affects G protein-coupled receptors and oxidoreductase activity. Results: Results indicate that NAR and OLE exhibit antitumor effects through multiple mechanisms by increasing miR-155-5p expression and inhibiting critical oncogenic targets in prostate cancer. Conclusions: Findings suggest that the dietary intake of these natural compounds (citrus and olive products) should be considered in prostate cancer prevention strategies, shedding light on the epigenetic mechanisms of polyphenols in cancer treatment and contributing to the development of new therapeutic strategies.

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