Involvement of ABC transporters in the detoxification of non-substrate nanoparticles in lung and cervical cancer cells

Toxicology. 2021 Mar 22:152762. doi: 10.1016/j.tox.2021.152762. Online ahead of print.ABSTRACTThis paper aimed to systemically investigate the role of adenosine triphosphate-binding cassette (ABC transporters) in the detoxification of non-substrate nanoparticles including titanium dioxide (n-TiO2, 5-10 nm) and gold (AuNPs, 3 nm, 15 nm, and 80 nm, named as Au-3, Au-15 and Au-80) in human lung cancer (A549) and human cervical cancer (HeLa) cells. All these nanoparticles were of larger hydrophilic diameters than the channel sizes of ABC transporters, thus should not be the substrates of membrane proteins. After 24-h treatment, they induced significant cytotoxicity as reflected by the reduction in cell viability and glutathione (GSH) contents, as well as the increase in reactive oxygen species (ROS) level. At median-lethal concentrations (10 mg/L n-TiO2, 2 mg/L Au-3, 5 mg/L Au-15, and 10 mg/L Au-80 for A549 cells; 20 mg/L n-TiO2, 2 mg/L Au-3, 5 mg/L Au-15, and 10 mg/L Au-80 for Hela cells), all the nanoparticles significantly induced the gene expressions and activities of ABC transporters including P-glycoprotein (PGP) and multidrug resistance associated protein 1 (MRP1). Addition of transporter inhibitors enhanced the ROS levels produced by nanoparticles, but didn't alter their death-inducing effects and intracellular accumulations. With specific suppressors, transcription factors like nuclear factor-erythroid 2-related factor-2 (NRF2) and pregnane X receptor (PXR) were proved t...
Source: Toxicology - Category: Toxicology Authors: Source Type: research