Investigating the role of calcium and biological trace elements in hypericin photodynamic therapy induced tumor cell death using nuclear microscopy

Abstract

Photodynamic therapy (PDT) is a promising new modality for the treatment of several types of cancer, including nasopharyngeal carcinoma (NPC). It involves the use of a photosensitising drug together with exposure to light to kill tumor cells via the generation of reactive oxygen species (ROS). Since transition trace metal ions such as iron are required in the generation of ROS in biological systems, it is possible that they also play a role in PDT-induced cell death. Additionally, some studies also show the involvement of calcium in PDT-induced apoptosis. Thus both major and trace biological elements may be involved in PDT cell killing mechanisms. This study involves the analysis of human NPC xenograft tumors in murine models using the National University of Singapore nuclear microscope. PDT was carried out using the photosensitiser hypericin under various conditions. The microbeam techniques of particle induced X-ray emission, Rutherford backscattering spectrometry and scanning transmission ion microscopy were used to quantify elemental concentrations in cryo-fixed sections of tumor tissue. Preliminary results are presented as well as their implications for the mechanisms underlying photodynamic cell killing. © 2005 Elsevier B.V. All rights reserved.