USE OF NATURAL COMPOUNDS SPECIFICALLY STILBENOIDS AND FLAVONOIDS TO OVERCOME CHEMOTHERAPY RESISTANCE IN BREAST CANCER CELLS MECHANISMS

Abstract

Objectives of the study were to find the exact molecular routes by means of which stilbenoids and to maximize their effectiveness as supplementary treatments in defeating resistance to chemotherapy in breast cancer. For this purpose, the study employs an integrated in vitro-in vivo approach, involving the selection of representative compounds, development of chemotherapy-resistant cell lines, assessment of apoptosis and molecular pathways, determination of bioavailability and pharmacokinetics, and evaluation of in vivo efficacy. Key aspects include transcriptomic and proteomic profiling, functional validation experiments, nanocarrier optimization, and detailed statistical analysis. The study design and methods are aligned with established guidelines and ethical considerations to ensure the scientific rigor and validity of the findings. It demonstrated that the additive effect of pterostilbene is abrogated when AKT1 is knocked down, indicating that the inhibition of Akt is a primary mechanism through which the natural compound exerts its chemo sensitizing properties. These have successfully encapsulated pterostilbene into PLGA nanoparticles, resulting in a dramatic 5.8-fold increase in the area under the curve (AUC) and a 3.3-fold improvement in the absolute oral bioavailability compared to the free drug. The nanoformulation resulted in a dramatic 5.8-fold increase in AUC and an absolute oral bioavailability of 87.2%, representing a 3.3-fold improvement over the free drug. This comprehensive approach represents a significant advancement in overcoming chemoresistance in breast cancer.