Mitochondrion-targeted photosensitizer enhances the photodynamic effect-induced mitochondrial dysfunction and apoptosis

Tsung I. Peng, Cheng Jen Chang, Mei Jin Guo, Yu Huai Wang, Jau Song Yu, Hong Yueh Wu, Mei Jie Jou

研究成果: 雜誌貢獻文章

47 引文 (Scopus)

摘要

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.
原文英語
頁(從 - 到)419-428
頁數10
期刊Annals of the New York Academy of Sciences
1042
DOIs
出版狀態已發佈 - 一月 1 2005
對外發佈Yes

指紋

Mitochondria
Photosensitizing Agents
Apoptosis
Laser beam effects
Lasers
Reactive Oxygen Species
Coloring Agents
Mitochondrial Swelling
Phototoxic Dermatitis
verteporfin
Derivatives
Ring
Propidium
Negotiating
In Situ Nick-End Labeling
Cell death
Cell membranes
Confocal Microscopy
Glioma
Toxicity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

引用此文

Mitochondrion-targeted photosensitizer enhances the photodynamic effect-induced mitochondrial dysfunction and apoptosis. / Peng, Tsung I.; Chang, Cheng Jen; Guo, Mei Jin; Wang, Yu Huai; Yu, Jau Song; Wu, Hong Yueh; Jou, Mei Jie.

於: Annals of the New York Academy of Sciences, 卷 1042, 01.01.2005, p. 419-428.

研究成果: 雜誌貢獻文章

Peng, Tsung I. ; Chang, Cheng Jen ; Guo, Mei Jin ; Wang, Yu Huai ; Yu, Jau Song ; Wu, Hong Yueh ; Jou, Mei Jie. / Mitochondrion-targeted photosensitizer enhances the photodynamic effect-induced mitochondrial dysfunction and apoptosis. 於: Annals of the New York Academy of Sciences. 2005 ; 卷 1042. 頁 419-428.
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abstract = "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.",
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T1 - Mitochondrion-targeted photosensitizer enhances the photodynamic effect-induced mitochondrial dysfunction and apoptosis

AU - Peng, Tsung I.

AU - Chang, Cheng Jen

AU - Guo, Mei Jin

AU - Wang, Yu Huai

AU - Yu, Jau Song

AU - Wu, Hong Yueh

AU - Jou, Mei Jie

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AB - 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.

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KW - Reactive oxygen species

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