Mitochondrial photodamages by ALA-PDT result in cytoskeleton reorganization
Date Issued
2004
Date
2004
Author(s)
Wu, Chia-Lun
DOI
zh-TW
Abstract
Photodynamic Therapy (PDT) is the new modality for cancer treatment, which involves photosensitiser excited by specific wavelength of light. 5-Aminolevulinic acid (5-ALA), a precursor in the heme biosynthetic pathway and of the subsequently activated photosensitiser, shows selective damage to tumor tissue after light irradiation. Studies have shown that 5-ALA is metabolized to protoporphrin IX, which selectively accumulates to greater extent in tumor cells and exhibits its cytotoxicity via singlet oxygen and ROS after irradiation of 630 nm light source. Using mouse embryonic fibroblast cells (NIH3T3), we found ALA was metabolized to PpIX in mitochondria by confocal microscope and the accumulation of PpIX reached to its plateau within 3 hr.
After ALA-PDT, quantity of ROS and singlet oxygen were generated within the cells and consequently caused mitochondrial swelling which led to mitochondrial damage. Further studies have shown photo-induced mitochondrial damages with supporting evidences as following: (1) reduced mitochondria dehydrogenase activity (2) breakdown of mitochondrial membrane potential, and (3) decreased intracellular ATP content. These evidences indicate that ALA-based PDT induces photocytoxicity via selective mitochondrial damage.
Meanwhile, following ALA-PDT, cells exhibit dramatically morphological change and decrease deattachment to substratum by trypsinization. The pattern of resistance to trypsinization following ALA-PDT was in a dose-dependent manner and gradually reversed post ALA-PDT. Moreover, the cytoskeleton, actin, and cytoskeleton adaptor protein, paxillin, vinculin, and
Subjects
細胞骨架重組
五胺基酮戊酸
光動力效應: 粒線體傷害
cytoskeleton
ALA-PDT
mitochondria
SDGs
Type
other
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