Studies of the Biological Effects of 5-Aminolevulinic Acid Photodynamic Therapy-Induced Mitochondrial Damage in PC12 Cells
Date Issued
2004
Date
2004
Author(s)
Tseng, Chia-Yi
DOI
zh-TW
Abstract
Photodynamic therapy (PDT) has been developed as a modality for cancer treatment, which is based on the administration of photosensitizers to induce cytotoxicity after light irradiation. It has been shown that singlet oxygen and other reactive oxygen species (ROS) are responsible for the PDT induced cell killing that leads to tumor ablation. As the primary oxidant associated with the PDT reaction is singlet oxygen, photosensitization has been found to oxidize cellular macromolecules including lipids, proteins, and nucleic acids that result in cell death. 5-aminolevulinic acid (ALA) has been successfully used to diagnose and treat neoplastic tissue. ALA itself is not a photosensitizer and serves as the biological precursor of the endogenous photosensitizers, protoporphyrin IX (PpIX), in the heme biosynthetic pathway. It has been shown that ALA–PDT induced selective destruction of neoplastic lesions attribute to the aberration of heme biosynthesis, such as the reduction of ferrochelatase (FC) activities, in tumor cells. Rat pheochromocytoma cells (PC12 cells), a kind of tumor cell, is a useful model of studying in neurobiology and neurochemistry. The purpose of this study is to investigate the effects of ALA-PDT induced mitochondrial damage in PC12 cells. We found: (1) ALA-PDT results in mitochondrial dysfunctions as indicated by the decreased activity of mitochondrial dehydrogenase, reduced ability of ATP generation and disruption of membrane potential. (2)ALA-PDT induced apoptotic death of PC12 cells judged by Hoechst 33258 and TUNEL staining. (3) After 5 times of ALA-PDT (5PDT) treatment, mitochondrial function has changed as indicated by the decreased ability of ATP generation and membrane potential. Moreover, the differentiation ability of PC12 cells has reduced and inhibited. (4) ALA-PDT results in the disruption of membrane potential in differentiated PC12 cells. (5)ALA-PDT caused neurite damage by morphology and microtubules immunostaining observation in PC12 cells.
Subjects
ＰＣ12細胞
粒線體
五胺基酮戊酸光動力效應
PC12 Cells
5-Aminolevulinic Acid Photodynamic Therapy
Mitochondria
SDGs
Type
other
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