TiO2 particles induce ER stress and apoptosis in human hepatoma cells, HepG2, in a particle size-dependent manner

  • Ha Na Song
  • Su Kyung Jang
  • Ok Kyung Hwang
  • Hong Jin Lee
  • Hyang Sook ChunEmail author


The cytotoxicity of TiO2 nanoparticles are well-known, but the particle size-dependent induction of ER stress and apoptosis by TiO2 in hepatocytes has not been elucidated clearly. In the present study, we investigated whether a fine TiO2 particle and two types of TiO2 nanoparticles induce ER stress and apoptosis differently in HepG2 cells. A particle size-dependent decrease in cell viability was observed after exposure to the TiO2 particles. The levels of ER stress-related proteins (BiP, CHOP, ATF6α, and p-PERK) were increased with decreasing particle size. TiO2 particles induced ER stress-mediated apoptosis in a particle size-dependent manner as seen by a decrease in the expression of Bcl-2, and increases in the expression of Bax, caspase-12, and cleaved caspase-3. These results indicated that the cytotoxicity produced by TiO2 particles was related to particle size, with smaller TiO2 nanoparticles producing greater toxic effects involving ER stress and apoptosis in the HepG2 cells.


Apoptosis ER HepG2 Size-dependent TiO2 



This work was supported by the Bio-Synergy Research Project (NRF-2013M3A9C4078156) of the Ministry of Science and by the Chung-Ang University Graduate Research Scholarship.

Compliance with ethical standards

Conflicts of interest

The authors declare no conflict of interest.


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Copyright information

© The Korean Society of Food Science and Technology 2019

Authors and Affiliations

  • Ha Na Song
    • 1
  • Su Kyung Jang
    • 1
  • Ok Kyung Hwang
    • 2
  • Hong Jin Lee
    • 1
  • Hyang Sook Chun
    • 1
    Email author
  1. 1.Advanced Food Safety Research Group, BK21 Plus, School of Food Science and TechnologyChung-Ang UniversityAnseongKorea
  2. 2.New Drug Development CenterOsong Medical Innovation FoundationCheongjuKorea

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