Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 138, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2021.111409
Keywords
MCF-7; Piceatannol; Nanospheres; Breast cancer; Zein; Apoptosis; Cell cycle; Diffusion; Cytotoxicity
Funding
- Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, Saudi Arabia [G: 224-130-1440]
- DSR
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The study demonstrates that PCT-ZN NSs have a significant inhibitory effect on MCF-7 cells, with higher cellular uptake, enhanced pro-apoptotic activity, and induction of oxidative stress.
Piceatannol (PCT), a natural polyphenolic stilbene, has pleiotropic pharmacological potentials. It possesses cytotoxic activities toward variant cancerous cells. Zein nanospheres (ZN NSs) have been introduced as ideal nanostructures due to their natural origin, safety, histocompatibility. and convenient method of formulation. The purpose of this study was to explore the impact of PCT-ZN NSs formula on pharmacotherapy potential of PCT against human breast cancer MCF-7 cells. PCT-ZN NSs were formulated and characterized selectively to particle size, zeta potential, encapsulation efficiency and diffusion of PCT. The selected formula has a particle size of 84.4 ? 2.3 nm, zeta potential value of 33.8 ? 1.2 mV and encapsulation efficiency of 89.5 ? 4.1%. PCT-ZN NSs displayed significantly lower IC50 against MCF-7 cells by about 24 folds. Further, PCT-ZN NSs formula showed higher cellular uptake as compared to free PCT. Examination of cell cycle phases displayed cells accumulation in G2-M phase and increased percentage cells in pre-G1 phase indicating an apoptosis-enhancing activity. Annexin V staining indicated augmented early and late apoptosis. PCT-ZN NSs pro-apoptotic activity was confirmed by the observed significant increased mRNA expression of CASP3, p53, and Bax as well as decreased expression of Bcl2. In addition, PCT-ZN NSs induced oxidative stress as evidenced by depletion of glutathione reductase (GR) activity, increased generation of reactive oxygen species (ROS) and accumulation of lipid peroxidation products. Conclusively, ZN nanostructures of PCT revealed superior cell death-inducing activities against MCF-7 cells in comparison with free PCT. This is mediated, at least partly, by enhanced cellular uptake, pro-apoptotic activity, and oxidative stress potential.
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