Abstract 69P
Background
Nucleolin (Ncl), a multifaceted RNA-binding domain protein, is overexpressed in various cancers and is associated with dysfunctions in cellular signaling pathways. Resveratrol (Res), a naturally occurring polyphenol, exhibits anti-cancer, anti-inflammatory, and antioxidant properties. In recent years, Res has grabbed significant attention for its ability to target molecular pathways in cancer, both alone and synergistically with conventional drugs. However, its clinical application is hindered by low solubility, poor pharmacokinetic properties, and instability. Engineered porous silicon (pSi) nanocarriers have emerged as an effective drug delivery system to overcome the intrinsic limitations of traditional cancer therapeutics.
Methods
In-vitro study was conducted to evaluate the efficacy of Res-loaded pSi in comparison to free-Res in targeting Ncl in breast cancer cells. This study included cytotoxicity assays, RT-PCR to assess Ncl mRNA expression, and analyses of apoptosis and cell cycle progression. Additionally, a confirmatory study to determine the potential of Resveratrol to target the RNA-binding domain (RBD) of Ncl was performed using in-silico methods.
Results
Res-loaded pSi demonstrated enhanced anti-proliferative effects with IC50 values of 70 μM and 100 μM in MCF-7 and MDA-MB231 cells, compared to 100 μM and 300 μM for free-Res. It significantly downregulated Ncl mRNA expression by 3.5-fold and 12.6-fold, compared to 1.6-fold and 3.5-fold with free Res in the respective cell lines. Additionally, Res-loaded pSi showed greater inhibition of cell proliferation, induction of apoptosis, and G1 phase cell cycle arrest at lower concentrations than free Res. Computational analysis confirmed Res as a potential target for the RBD domain of Ncl, with a binding free energy (ΔG) of -37.4842 kcal/mol and stable MD simulation of the ligand-protein complex up to 1 microsecond.
Conclusions
Our study exemplifies the potential application of pSi with natural compounds like Res for next-generation drugs, hence establishing a new avenue in establishing Ncl targeted breast cancer therapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.