Enhancement of 5-Aminolevulinic acid-induced oxidative stress on two cancer cell lines by gold nanoparticles

Abstract

5-Aminolevulinic acid (5-ALA) and its methyl ester (5-ALA-Me) at mM concentration levels induce oxidative stress via the production of reactive oxygen species (ROS). Human cancer cell lines (MCF-7 and HepG2) incubated in the dark in the simultaneous presence of 5.0 mM or more 5-ALA or 5-ALA-Me (for MCF-7) and 7 µg/mL of 15 nm citrate capped gold nanoparticles (AuNPs) were damaged more seriously compared to those in the presence of the levulinic acid alone. Damage is visible in electron micrographs which reveal similar morphology both in the presence or absence of AuNPs. Cytotoxicity was observed irrespective of the presence of serum and medium. Production of ROS in cell free samples containing 5-ALA-Me was monitored by EPR as the DMPO-OH spin adduct and also showed a catalytic effect of AuNPs. Both SOD and CAT inhibited the production of ROS and also reduced cytotoxicity in the cell samples. These observations can be explained by initial attack on the cell membrane by ROS produced in the medium outside the cell and provide insight into possible uses of 5-ALA in cancer chemotherapy.

Keywords::

• Gold nanoparticles
• 5-Aminolevulinic acid
• cytotoxicity
• reactive oxygen species

Acknowledgements

We are grateful to Drs Murali C. Krishna, Hirofumi Matsui, Go Kagiya, Hisanari Ishii and Chie Kojima for valuable discussions. We acknowledge Mr Adam Harned for help with EM images. We thank to Drs Fuminori Hyodo and Shingo Matsumoto for supporting EPR studies. S.I. acknowledges a Visiting Fellowship from the Fogarty International Center, NIH. This research was supported by the Intramural Reseach Program of the NIH, National Cancer Institute, Center for Cancer Reseach, and was funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract NOI-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This paper was first published online on Early Online on 28 September 2009.