Phthalocyanine 4 photodynamic therapy-induced apoptosis of mouse L5178Y-R cells results from a delayed but extensive release of cytochrome c from mitochondria

Chiu, Song Mao; Evans, Helen H.; Lam, Minh; Nieminen, Anna‐Liisa; Oleinick, Nancy L.

doi:10.1016/s0304-3835(01)00422-0

Cited by 41 publications

(29 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In order to test a possible correlation between the loss of ∆Ψ m and cytochrome c release and apoptosis, 3 doses of PDT were chosen for this study; LY-R cells were treated with 300 nM Pc 4 and irradiated with either 60, 90 or 120 mJ/cm 2 red light. As determined by clonogenic assay, PDT with the lowest dose results in killing of 99% of the cells (Chiu et al, 2001). Figure 1 shows that all 3 PDT doses caused greater than 80% of the cells to undergo nuclear apoptosis within 1 h. An even higher incidence of apoptotic figures (92.3 ± 0.6%) was observed 2 h after these 3 doses of Pc 4-PDT, and extensive degradation of DNA to oligonucleosomesize fragments was detected at this time (not shown).…”

Section: Resultsmentioning

confidence: 99%

Dissociation of mitochondrial depolarization from cytochrome c release during apoptosis induced by photodynamic therapy

2001

View full text Add to dashboard Cite

Photodynamic therapy (PDT) with the phthalocyanine photosensitizer Pc 4 induces rapid apoptosis in mouse lymphoma (LY-R) cells, initiating with the release of cytochrome c from mitochondria. It has been proposed that the opening of the mitochondrial membrane permeability transition pores, which results in the dissipation of the mitochondrial membrane potential (Δψ m ), is essential for the escape of cytochrome c from mitochondria into the cytosol as well as for apoptotic cell death. Therefore, we have assessed the correlation between the loss of Δψ m and the release of cytochrome c following PDT. Treatment of LY-R cells with 300 nM Pc 4 and 60, 90 or 120 mJ/cm 2 of red light resulted in apoptosis of 80–90% of the cells, accompanied by >20-fold elevation in caspase-3-like activity within one h. At all 3 doses of PDT employed here, the majority of the cytochrome c was released from mitochondria at 15 min after irradiation, as determined by an immunohistochemical method. In contrast, the loss of Δψ m following PDT, as monitored by the uptake of JC-1 or Rh-123, depended on the PDT dose and the post-treatment time. In spite of the release of cytochrome c at 15 min after each of the 3 doses, a corresponding loss of Δψ m was observed only for those cells that received the highest dose of PDT. Virtually all cells that received one of the lower doses of PDT (300 nM Pc 4 plus 60 or 90 mJ/cm 2 ) maintained normal Δψ m . Hence, our results support the conclusion that the release of cytochrome c from mitochondria resulting from Pc 4-PDT-induced photodamage is independent of the loss of Δψ m . Therefore, it is important to consider a range of doses of this or other apoptotic stimuli in deciphering the relationship of metabolic responses that contribute to apoptosis. © 2001 Cancer Research Campaign http://www.bjcancer.com

show abstract

Section: Resultsmentioning

confidence: 99%

Dissociation of mitochondrial depolarization from cytochrome c release during apoptosis induced by photodynamic therapy

2001

View full text Add to dashboard Cite

show abstract

“…Preincubation of Jurkat cells with inhibitors of the mitochondrial permeability transition pore was also without effect on the loss of mitochondrial membrane potential induced by PDT with hypericin [69]. Interestingly, in mouse L5178Y-R cells exposed to low doses of PDT, cytochrome C was released from mitochondria without loss of mitochondrial membrane potential, suggesting that the release of cytochrome C is independent of the loss of mitochondrial membrane potential [70]. Photosensitization of hepatoma Hepa 1c1c7 cells with the lysosomal sensitizer Npe6 also induced the release of cytochrome C and activated caspase-9 and caspase-3-like activity before depolarization of the mitochondrial membrane [60].…”

Section: Role Of Caspases In Pdtmentioning

confidence: 91%

Intracellular signaling mechanisms in photodynamic therapy

Almeida

Manadas

Carvalho

et al. 2004

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

242

292

View full text Add to dashboard Cite

In photodynamic therapy (PDT) a sensitizer, light and oxygen are used to induce death of tumor cells and in the treatment of certain noncancerous conditions. Cell death in PDT may occur by apoptosis or by necrosis, depending on the sensitizer, on the PDT dose and on the cell genotype. Some sensitizers that have been used in PDT are accumulated in the mitochondria, and this may explain their efficiency in inducing apoptotic cell death, both in vitro and in vivo. In this review we will focus on the events that characterize apoptotic death in PDT and on the intracellular signaling events that are set in motion in photosensitized cells. Activation of phospholipases, changes in ceramide metabolism, a rise in the cytosolic free Ca 2 + concentration, stimulation of nitric oxide synthase (NOS), changes in protein phosphorylation and alterations in the activity of transcription factors and on gene expression have all been observed in PDT-treated cells. Although many of these metabolic reactions contribute to the demise process, some of them may antagonize cell death. Understanding the signaling mechanisms in PDT may provide means to modulate the PDT effects at the molecular level and potentiate its antitumor effectiveness. D

show abstract

“…10 PDT is an efficient inducer of apoptosis, with the initiating reactions dependent upon the preferential sites of photosensitizer localization. PDT with the silicon phthalocyanine Pc 4 or with other mitochondrion-targeted photosensitizers causes rapid cytochrome c release from mitochondria, caspase activation, PARP cleavage, chromatin condensation and DNA fragmentation [11][12][13][14][15][16][17] ; reviewed in. 18 PDT promotes Bax activation, which includes conformational change (exposure of an epitope detected by the 6A7 antibody) as well as translocation from the cytosol to mitochondria immediately or shortly after PDT.…”

Section: Introductionmentioning

confidence: 99%

Photodynamic therapy-induced death of HCT 116 cells: Apoptosis with or without Bax expression

et al. 2005

View full text Add to dashboard Cite

Cell death following photodynamic therapy (PDT) with the photosensitizer Pc 4 involves the intrinsic pathway of apoptosis. To evaluate the importance of Bax in apoptosis after PDT, we compared the PDT responses of Bax-proficient (Bax(+/-)) and Bax knock-out (BaxKO) HCT116 human colon cancer cells. PDT induced a slow apoptotic process in HCT Bax(+/-) cells following a long delay in the activation of Bax and release of cytochrome c from mitochondria. Although cytochrome c was not released from mitochondria following PDT in BaxKO cells, an alternative mechanism of caspase-dependent apoptosis with extensive chromatin and DNA degradation was found in these cells. This alternative process was less efficient and slower than the normal apoptotic process observed in Bax(+/-) cells. Early events upon PDT, such as the loss of mitochondrial membrane potential, photodamage to Bcl-2, and activation of p38 MAP kinase, were observed in both HCT116 cell lines. In spite of differences in the efficiency and mode of apoptosis induced by PDT in the Bax(+/-) and BaxKO cells, they were found to be equally sensitive to killing by PDT, as determined by loss of clonogenicity. Thus, for Pc 4-PDT, the commitment to cell death occurs prior to and independent of Bax activation, but the process of cellular disassembly differs in Bax-expressing vs. non-expressing cells.

show abstract

Phthalocyanine 4 photodynamic therapy-induced apoptosis of mouse L5178Y-R cells results from a delayed but extensive release of cytochrome c from mitochondria

Cited by 41 publications

References 20 publications

Dissociation of mitochondrial depolarization from cytochrome c release during apoptosis induced by photodynamic therapy

Dissociation of mitochondrial depolarization from cytochrome c release during apoptosis induced by photodynamic therapy

Intracellular signaling mechanisms in photodynamic therapy

Photodynamic therapy-induced death of HCT 116 cells: Apoptosis with or without Bax expression

Contact Info

Product

Resources

About