Titanium Dioxide Nanoparticles Induced HeLa Cell Necrosis under UVA Radiation through the ROS-mPTP Pathway

Abstract

Titanium dioxide nanoparticles (nano-TiO2), as a common nanomaterial, are widely used in water purification, paint, skincare and sunscreens. Its safety has always been a concern. Prior studies have shown that ultraviolet A (UVA) can exacerbate the toxicity of nano-TiO2, including inducing cell apoptosis, changing glycosylation levels, arresting cell cycle, inhibiting tumor cell and bacterial growth. However, whether the combination of UVA and nano-TiO2 cause cell necrosis and its mechanism are still rarely reported. In this study, we investigated the cytotoxicity and phototoxicity of mixture crystalline nano-TiO2 (25% rutile and 75% anatase, 21 nm) under UVA irradiation in HeLa cells. Our results showed that the abnormal membrane integrity and the ultrastructure of HeLa cells, together with the decreased viability induced by nano-TiO2 under UVA irradiation, were due to cell necrosis rather than caspase-dependent apoptosis. Furthermore, nano-TiO2 and UVA generated the reactive oxygen species (ROS) and caused the mitochondrial permeability transition pore (mPTP) of HeLa cells to abnormally open. Cell viability was significantly increased after adding vitamin C (VC) or cyclosporin A (CsA) individually to inhibit ROS and mPTP. Clearance of ROS could not only impede the opening of mPTP but also reduce the rate of cell necrosis. The results suggest the possible mechanism of HeLa cell necrosis caused by nano-TiO2 under UVA irradiation through the ROS-mPTP pathway.

Titanium Dioxide Induces Apoptosis under UVA Irradiation via the Generation of Lysosomal Membrane Permeabilization-Dependent Reactive Oxygen Species in HaCat Cells

“…As cell viability decreases after TiO 2 NP and UVA treatment, we explored the mode of death of these cells. The photocatalytic activity of TiO 2 NPs can induce apoptosis and necrosis through various mechanisms [ 67 , 68 , 70 , 71 , 72 ]. Apoptosis is a form of programmed cell death characterized by caspase activation, cell contraction, apoptotic body formation, exposure outside the cell membrane, chromatin condensation, and DNA fragmentation [ 73 , 74 , 75 ].…”

Titanium dioxide induces apoptosis under UVA irradiation via the generation of lysosomal membrane permeabilization-dependent reactive oxygen species in HaCaT cells

“…As cell viability decreases after TiO 2 NP and UVA treatment, we explored the mode of death in these cells. The photocatalytic activity of TiO 2 NPs can induce apoptosis and necrosis through various mechanisms [54][55][57][58][59]. Apoptosis is a form of programmed cell death characterized by caspase activation, cell contraction, apoptotic body formation, exposure outside the cell membrane, chromatic condensation, and DNA fragmentation [60][61][62].…”

Algae Metabolites as an Alternative in Prevention and Treatment of Skin Problems Associated with Solar Radiation and Conventional Photo-protection

“…Although nanoparticles of inorganic filters were a cosmetic solution in aesthetic, titanium dioxide nanoparticles (nano-TiO 2 ) present several problems. nano-TiO 2 was tested on pig ears skin like this way particle´s penetration through the stratum was found and they exhibit increases its toxicity in the presence of UVA causing effects like cell apoptosis, changes in glycosylation levels and arresting cell cycle (Geng et al, 2020). The ROS generation is the mechanism through cell toxicity that occur since these inorganic articles in UVR generate these reactive species which have the ability to alter cell homeostasis by oxidizing molecules like lipid, protein, nucleic acid, or other biomolecules (Geng et al, 2020).…”