TY - JOUR

T1 - Oxidative stress-mediated cytotoxicity and apoptosis induction by TiO₂ nanofibers in HeLa cells

A1 - Ramkumar,Kunga Mohan

A1 - Manjula,Chinnasamy

A1 - GnanaKumar,Georgepeter

A1 - Kanjwal,Muzafar Ahmed

A1 - Sekar,Thillai V.

A1 - Paulmurugan,Ramasamy

A1 - Rajaguru,Palanisamy

AU - Ramkumar,Kunga Mohan

AU - Manjula,Chinnasamy

AU - GnanaKumar,Georgepeter

AU - Kanjwal,Muzafar Ahmed

AU - Sekar,Thillai V.

AU - Paulmurugan,Ramasamy

AU - Rajaguru,Palanisamy

PB - Elsevier BV

PY - 2012

Y1 - 2012

N2 - Titanium dioxide nanoparticles are increasingly being used in pharmaceutical and cosmetic products. The high aspect ratio of fibrous nanomaterials, such as carbon nanotubes and TiO2 nanofibers (TiO2NFs), similar to the one used in this study makes them an attractive structural material and has attracted a lot of attention due to their possible negative health effects as suggested by their morphological similarities with asbestos. In the present study, therefore, toxicity of TiO2NFs was evaluated in human cervical adenocarcinoma HeLa cells. The TEM and XRD analyses showed that TiO2NFs used in this study are pure with uniform diameter of around 200 nm, and their length to width aspect ratio ranged between 5 and 15. Exposure of HeLa cells to TiO2NFs induced significant cytotoxicity even at doses as low as 2 μg/ml. The intracellular uptake of TiO2NFs in cells was shown by Alizarin Red S (ARS) labeled nanofibers. The mechanism of toxicity is mainly due to the induction of cellular oxidative stress, as revealed by elevated ROS levels, reduced antioxidant levels, and increased lipid peroxidation leading to apoptosis. The cell cycle analysis indicated G2/M cell cycle arrest in the cells exposed to TiO2NF. TiO2NFs treatment to HeLa cells resulted in increased expression of proapoptotic proteins Bax with an increase in cytosolic Cytochrome-C and inhibition of anti-apoptotic protein Bcl-2. Our results revealed the potential mechanism of cellular effects of TiO2NFs.

AB - Titanium dioxide nanoparticles are increasingly being used in pharmaceutical and cosmetic products. The high aspect ratio of fibrous nanomaterials, such as carbon nanotubes and TiO2 nanofibers (TiO2NFs), similar to the one used in this study makes them an attractive structural material and has attracted a lot of attention due to their possible negative health effects as suggested by their morphological similarities with asbestos. In the present study, therefore, toxicity of TiO2NFs was evaluated in human cervical adenocarcinoma HeLa cells. The TEM and XRD analyses showed that TiO2NFs used in this study are pure with uniform diameter of around 200 nm, and their length to width aspect ratio ranged between 5 and 15. Exposure of HeLa cells to TiO2NFs induced significant cytotoxicity even at doses as low as 2 μg/ml. The intracellular uptake of TiO2NFs in cells was shown by Alizarin Red S (ARS) labeled nanofibers. The mechanism of toxicity is mainly due to the induction of cellular oxidative stress, as revealed by elevated ROS levels, reduced antioxidant levels, and increased lipid peroxidation leading to apoptosis. The cell cycle analysis indicated G2/M cell cycle arrest in the cells exposed to TiO2NF. TiO2NFs treatment to HeLa cells resulted in increased expression of proapoptotic proteins Bax with an increase in cytosolic Cytochrome-C and inhibition of anti-apoptotic protein Bcl-2. Our results revealed the potential mechanism of cellular effects of TiO2NFs.

KW - TiO2

KW - Nanofiber

KW - Apoptosis

KW - HeLa cells

KW - Cytotoxicity

KW - Nanoparticles

U2 - 10.1016/j.ejpb.2012.02.013

DO - 10.1016/j.ejpb.2012.02.013

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

IS - 2

VL - 81

SP - 324

EP - 333

ER -