Paclitaxel Nanoparticles Induce Apoptosis and Regulate TXR1, CYP3A4 and CYP2C8 in Breast Cancer and Hepatoma Cells

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 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 as 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 phase. 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 13.1 g/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 to PTX-NPs, respectively, meanwhile the expression 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 cells resistance to the PTX and its enhanced metabolism.

The efficiency of MSC‐based targeted AIE nanoparticles for gastric cancer diagnosis and treatment: An experimental study

“…The initial rapid release of PTX from the NPs at pH 5.7 was partially due to the rapid degradation of the PCL‐PEG copolymers under acidic conditions and partially attributed to the carboxylic groups' protonation in the PCL‐PEG copolymers, which weakened the electrostatic interactions between the cationic PTX and the anionic polymer carrier 32,33 . Intensely hydrophobic interaction between PTX and PCL led to the slow‐release phase 34 . The rapid release under a lower pH condition favors the release of PTX from NPs in the acidic environment of the endo/lysosomes in the tumor cells, thus exerting a therapeutic function.…”

“…32,33 Intensely hydrophobic interaction between PTX and PCL led to the slow-release phase. 34 The rapid release under a lower pH condition favors the release of PTX from NPs in the acidic environment of the endo/lysosomes in the tumor cells, thus exerting a therapeutic function.…”

Insight into the role of clathrin‐mediated endocytosis inhibitors in SARS‐CoV‐2 infection

“… 59 Barbadin also affects cellular viability and induces both apoptosis and autophagy in breast cancer cells. 84 , 85 , 86 , 87 , 88 This may give genetic inhibitors more leverage to avoid the anticipated adverse effects of chemical inhibitors. Genetic inhibitors are used to inhibit CME by suppressing the expression of specific endocytic proteins.…”

“…Barbadin, for example, is a selective inhibitor of β ‐arrestin/AP2 interaction, 83 ERK1/2, and cAMP accumulation in human embryonic kidney cells 59 . Barbadin also affects cellular viability and induces both apoptosis and autophagy in breast cancer cells 84‐88 . This may give genetic inhibitors more leverage to avoid the anticipated adverse effects of chemical inhibitors.…”

Noncoding RNAs and their therapeutics in paclitaxel chemotherapy: Mechanisms of initiation, progression, and drug sensitivity

“…Different strategies have been applied to overcome PTX resistance, for instance by loading PTX onto nanoparticles to promote its targeted delivery and accumulation in tumors. Nanostructures can significantly enhance the efficacy of PTX chemotherapy and are associated with apoptosis induction in cancer cells (Diab, Alkafaas, et al, 2020; Fraguas‐Sánchez, Fernández‐Carballido, et al, 2020; Tang, Chen, et al, 2020). Another strategy is to combine PTX with drugs to suppress PTX resistance and overcome drug efflux from cancer cells (Attia, El‐Kersh, et al, 2020; Khan, Quispe, et al, 2020; Saghatelyan, Tananyan, et al, 2020; Zhang, Huang, et al, 2020).…”