Title:Paclitaxel Nanoparticles Induce Apoptosis and Regulate TXR1, CYP3A4 and CYP2C8 in Breast Cancer and Hepatoma Cells
Volume: 20
Issue: 13
Author(s): Thoria Diab, Samar S. Alkafaas, Thanaa I. Shalaby and Mohamed Hessien*
Affiliation:
- Department of Chemistry, Division of Biochemistry, Faculty of Science, Tanta University, Tanta,Egypt
Keywords:
Breast cancer, paclitaxel nanoparticles, PLGA, taxol resistance gene, CYPs, apoptosis.
Abstract:
Background and Objective: Although the anticancer potentials of water-insoluble drugs are
improved by nanoformulation, other intervening factors may contribute in the drug efficacy. This work was
designated to explore the effect of paclitaxel-loaded Poly(Lactic-co-Glycolic Acid) (PLGA) nanoparticles on the
viability of cancer cells, the expression of Taxol Resistance gene I (TXR1) and paclitaxel metabolizing genes.
Methods: Paclitaxel loaded PLGA Nanoparticles (PTX-NPs) were prepared, physically characterized and used
in the treatment of breast adenocarcinoma cells (MCF-7) and hepatoma cells (HepG2). Cells viability and apoptosis
were investigated. In parallel, RNA was isolated, reverse transcribed and used to monitor the expression
levels of TXR1, CYP 3A4 and CYP2C8 genes.
Results: PTX-NPs were characterized by transmission electron microscopy to be of a nano-size sphere-like
shape. FTIR analysis revealed good coupling between PTX and PLGA. The encapsulation efficiency was 99%
and the drug release demonstrated a progressive releasing phase followed by slower and sustained releasing
phases. Although HepG2 cells demonstrated more resistance to PTX than MCF-7 cells, both cell types were
more responsive to PTX-NPS compared to PTX. The IC50 values decreased from 19.3 to 6.7 in breast cancer cells
and from 42.5 to 13.1μg/ml in hepatoma cells. The apoptosis was the key mechanism in both cells, where at
least 44% of cells underwent apoptosis. The expression of TXR1 decreased when either cells were treated with
PTX-NPs, respectively, meanwhile the expressions of CYP3A4 and CYP2C8 were increased.
Conclusion: Taken together, this in vitro study reports the associations between the enhanced responsiveness of
MCF-7 and HepG2 cells to PLGA-loaded paclitaxel nanoparticles and the accompanying decrease in the cells
resistance to the PTX and its enhanced metabolism.
