In:
Annals of the New York Academy of Sciences, Wiley, Vol. 1042, No. 1 ( 2005-05), p. 419-428
Abstract:
A bstract : Recently, the mitochondrion has been considered as a novel pharmacological target for anticancer therapy due to its crucial role involved in arbitrating cell apoptosis. We have previously demonstrated that 488‐nm laser irradiation induced a specific mitochondrial reactive oxygen species (mROS) formation and apoptotic death. In this study, we used a second generation of photosensitizers, the benzoporphyrin‐derivative monoacid ring A (BPD‐MA). We investigated specifically mechanisms at the mitochondrial level for BPD‐MA coupled with 690‐nm laser irradiation, the photodynamic effect (PDE) of BPD‐MA, using conventional and laser scanning imaging microscopy in intact C6 glioma cells. We demonstrated BPD‐MA localized mainly in the mitochondrial area. The phototoxicity induced by 1∼10 J 690‐nm laser irradiation was minor as compared to that induced by 488‐nm laser irradiation. Unlike other mitochondrion‐targeted photosensitizers, the dark toxicity induced by BPD‐MA (0.05∼5 mg/mL, effective doses used for the PDE) was relatively low. Nevertheless, the PDE of BPD‐MA using 0.5 mg/mL coupled with 5J 690‐ nm irradiation induced profound and rapid ( 〈 1 min) mitochondrial swelling, mROS formation, and severe plasma membrane blebing as compared to that induced by 488‐nm laser irradiation ( 〈 10 min). Later, the PDE of BPD‐MA resulted in positive propidium iodide cell‐death stain and positive TUNEL apoptotic nuclear stain and DNA laddering. Finally, the PDT of BPD‐MA also instantaneously promoted the mitochondrion to diminish its covalent binding with a mitochondrial marker, MitoTracker Green. We conclude that the PDT of BPD‐MA targeted primarily and compellingly the mitochondrion to induce effective mitochondria‐mediated apoptosis and thus may serve as a powerful photosensitizer for clinical cancer therapy.
Type of Medium:
Online Resource
ISSN:
0077-8923
,
1749-6632
DOI:
10.1196/annals.1338.035
Language:
English
Publisher:
Wiley
Publication Date:
2005
detail.hit.zdb_id:
2834079-6
detail.hit.zdb_id:
211003-9
detail.hit.zdb_id:
2071584-5
SSG:
11
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