Evaluating the in vitro and in vivo effects of carvacrol zinc oxide quantum dots in breast cancer

J Biomater Sci Polym Ed. 2024 Dec 3:1-20. doi: 10.1080/09205063.2024.2429325. Online ahead of print.

Abstract

The study investigates the molecular interactions and biological effects of carvacrol zinc oxide quantum dots (CVC-ZnO QDs) on breast cancer in vitro MCF-7 cell lines and in vivo mammary cancer models. Molecular docking using AutoDock Vina revealed binding energies of CVC with key proteins in the PI3K/AKT/mTOR pathway, including PI3K, AKT, PTEN, and mTOR. The results showed significant interaction with specific amino acids, indicating a strong binding affinity. In vitro studies demonstrated a dose-dependent cytotoxic effect of CVC-ZnO QDs on MCF-7 cells, with an IC50 of 20.02 µg/mL, while enhancing intracellular reactive oxygen species (ROS) and decreasing mitochondrial membrane potential (MMP), indicative of apoptosis induction. Antioxidant activity, lipid peroxidation, and nuclear morphological changes were assessed, revealing decreased antioxidant status and increased lipid peroxidation in treated cells. In vivo, CVC-ZnO QDs modulated the PI3K/AKT/mTOR signaling in DMBA-induced mammary cancer in rats, decreasing p-PI3K, p-AKT, and p-mTOR expression while upregulating PTEN. Immunohistochemistry, qRT-PCR, and Western blot analyses confirmed these molecular alterations. The study concludes that CVC-ZnO QDs exert cytotoxic and pro-apoptotic effects on breast cancer cells by modulating the PI3K/Akt/mTOR pathway and promoting oxidative stress, presenting a potential therapeutic strategy for breast cancer management.

Keywords: Antioxidant; CVC-ZnO QDs; DMBA; MCF-7 cell line; PI3K/AKT/mTOR signaling; ROS; mammary carcinogen.

Plain language summary

CVC exhibited strong binding energy with proteins in the PI3K/Akt/mTOR pathway, suggesting potential cancer pathway modulation.CVC-ZnO QDs showed dose-dependent cytotoxicity on MCF-7 breast cancer cells by enhancing ROS production, reducing MMP, and inducing apoptosis.CVC-ZnO QDs increased lipid peroxidation and depleted antioxidant defenses, promoting cancer cell death.In DMBA-induced rat models, CVC-ZnO QDs downregulated PI3K, AKT, and mTOR expression while upregulating PTEN.