Titanium dioxide nanoparticles induce mitochondria-associated apoptosis in HepG2 cells

Area of Science:

• Nanotechnology
• Cell Biology
• Biochemistry

Background:

• Nanosized materials, including titanium dioxide (TiO2) nanoparticles, have widespread applications.
• Understanding their biological effects and potential hazards is crucial.
• TiO2 nanoparticles are extensively used, necessitating research into their impact on human cells.

Purpose of the Study:

• To investigate the biological effects of TiO2 nanoparticles (TiO2 NPs) on human liver cell lines (L02 and HepG2).
• To analyze the impact of TiO2 NPs on cell growth, proliferation, cell cycle, and apoptosis.
• To determine the molecular mechanisms underlying TiO2 NP-induced cellular changes, focusing on apoptosis and mitochondrial pathways.

Main Methods:

• Co-culture of normal liver (L02) and hepatoma (HepG2) cell lines with TiO2 NPs.
• Analysis of cell growth, proliferation, cell cycle, and apoptosis rates.
• Western blot analysis for apoptosis-associated proteins (caspase-3, αENaC) and mitochondria-related proteins (SIRT3, VDAC1, ACSS1).
• Assessment of mitochondrial membrane potential and ADP/ATP ratio.
• Validation using a nude mouse xenograft model.

Main Results:

• TiO2 NPs inhibited HepG2 cell growth, proliferation, and S-phase progression, while inducing apoptosis in a concentration-dependent manner.
• L02 cells showed no significant effects on growth, proliferation, apoptosis, or cell cycle.
• In HepG2 cells, TiO2 NPs upregulated caspase-3, αENaC, SIRT3, and VDAC1, and downregulated ACSS1.
• Mitochondrial membrane depolarization and altered ADP/ATP ratio were observed in HepG2 cells.
• In vivo studies confirmed the upregulation of VDAC1 and SIRT3 and downregulation of ACSS1 in TiO2 NP-treated tissues.

Conclusions:

• TiO2 NPs exhibit selective toxicity towards hepatoma cells, inhibiting proliferation and inducing apoptosis.
• Apoptosis in HepG2 cells is mediated by regulating osmotic pressure, αENaC, VDAC1, mitochondrial membrane depolarization, and caspase-3 activation.
• The observed effects suggest TiO2 nanoparticles possess potential as a safe antitumor agent.