Mitochondrial and endoplasmic reticulum stress-induced apoptotic pathways are activated by 5-aminolevulinic acid-based photodynamic therapy in HL60 leukemia cells

Grebeňová, Dana; Kuželová, Kateřina; Smetana, Karel; Pluskalová, Michaela; Cajthamlová, H; Marinov, Iuri; Fuchs, Ota; Souček, J; Jarolím, Petr; Hrkal, Zbyněk

doi:10.1016/s1011-1344(02)00410-4

Cited by 107 publications

(93 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, the present data confirm that PDT induces apoptosis through this signalling pathway. However, although mitochondria have been shown to be a prime target of PDT with certain photosensitisers (Kessel and Luo, 1998), and PDT causes photodamage to mitochondrion-bound proteins, in particular Bcl-2 (Xue et al, 2001a) and Bcl-xL (Xue et al, 2003a), and to mitochondrial and endoplasmic reticulum membrane structure (Grebenova et al, 2003), the present data suggest that the photodamage is insufficient to cause the release of cytochrome c spontaneously through the outer mitochondrial membrane. The release needs the participation of Bax.…”

Section: Discussioncontrasting

confidence: 51%

Bax is essential for mitochondrion-mediated apoptosis but not for cell death caused by photodynamic therapy

et al. 2003

View full text Add to dashboard Cite

The role of Bax in the release of cytochrome c from mitochondria and the induction of apoptosis has been demonstrated in many systems. Using immunocytochemical staining, we observed that photodynamic therapy (PDT) with the photosensitiser Pc 4 induced Bax translocation from the cytosol to mitochondria, and the release of cytochrome c from mitochondria as early signalling for the intrinsic pathway of apoptosis in human breast cancer MCF-7c3 cells. To test the role of Bax in apoptosis, MCF-7c3 cells were treated with Bax antisense oligonucleotides, which resulted in as much as a 50% inhibition of PDT-induced apoptosis. In the second approach, Bax-negative human prostate cancer DU-145 cells were studied. Following PDT, the hallmarks of apoptosis, including the release of cytochrome c from mitochondria, loss of mitochondrial membrane potential, caspase activation, and chromatin condensation and fragmentation, were completely blocked in these cells. Restoration of Bax expression in DU-145 cells restored apoptosis, indicating that the resistance of DU-145 cells to PDT-induced apoptosis is due to the lack of Bax rather than to another defect in the apoptotic machinery. However, despite the inhibition of apoptosis, the Bax-negative DU-145 cells were as photosensitive as Bax-replete MCF7c3 cells, as determined by clonogenic assay. Thus, for Pc 4-PDT, the commitment to cell death occurs prior to Bax activation.

show abstract

Section: Discussioncontrasting

confidence: 51%

Bax is essential for mitochondrion-mediated apoptosis but not for cell death caused by photodynamic therapy

et al. 2003

View full text Add to dashboard Cite

show abstract

“…Also, expression of CrmA did not affect the kinetics of cytochrome C release Jurkat human lymphoma T cells [295] and procaspase-3 cleavage in a rat/mouse T cell hybridoma sensitized with hypericin [68], suggesting that caspase-8 does not play a major role in the demise process in this model. The activation of caspases in photosensitized cells leads to the cleavage of a number of other cell proteins, including Bap-31 (shuttle protein between the ER and the intermediate compartment and/or Golgi complex [71]), DNA-dependent protein kinase (catalytic subunit) (DNA-PK CS [75]), ICAD (inhibitor of caspase activated DNAse); prevents DNA fragmentation via binding to caspase-activated deoxyribonuclease [76]), focal adhesion kinase (FAK, a kinase involved in the regulation of cell adhesion [73]), lamins (structural components of the nuclear envelope [73]), PARP (poly(ADP-ribose) polymerase, a DNA repair enzyme [18,20,44,54,68,71,72,75,[77][78][79][80][81][82][83][84][85]) and Ras GTPase-activating protein (Ras-GAP, a negative regulator of the Ras signaling pathway [71]). DNA fragmentation in segments that are multiples of 180 -200 bp, another hallmark of apoptotic cell death [86], was also observed in PDT, using different cell types and sensitizers (Table 1).…”

Section: Role Of Caspases In Pdtmentioning

confidence: 99%

Intracellular signaling mechanisms in photodynamic therapy

Almeida

Manadas

Carvalho

et al. 2004

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

241

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

“…A produção de PpIX pela via de síntese de heme é duas a 10 vezes maior em células malignas ou pré-malignas do que em células normais (Kormeili et al, 2004 (Grebenová et al, 2003). A autofagia também tem sido associada a 5-ALA-PDT, por mecanismo ainda quase nada conhecido.…”

Section: óXido Nítrico Sintase Induzível (Inos)unclassified

“…Esses achados corroboram outros estudos que também observaram inibição dessas proteínas após a PDT (Rapozzi et al, 2011;Dewaele et al, 2011;Grebenová et al, 2003;Kim et al, 1999).…”

Section: Gruposunclassified

See 1 more Smart Citation

Resistência de células de carcinoma epidermóide bucal à terapia fotodinâmica mediada pelo ácido 5-aminolevulínico

Rosin¹

View full text Add to dashboard Cite

A minha Orientadora, Prof a . Dr a . Luciana Corrêa, por sempre ouvir e discutir comigo todas as questões e dúvidas que surgiram durante o desenvolvimento desta tese e por ser essa pessoa tão generosa, inteligente e acessível. Admiro-a muito como pessoa e pesquisadora.Ao Prof. Dr. Moacir Novelli, que durante suas visitas ao laboratório sempre alegrava meu dia e por compartilhar comigo um pouco da sua imensa sabedoria. A Marina, a única companheira de profissão da Pós, que sempre esteve disposta a me ajudar e me ouvir, pela amizade, carinho e companheirismo. Pelos nossos cafés da manhã que sempre tornava meu dia mais leve e agradável.A Karla, pelo bom humor constante que sempre alegrava meu dia, por sempre me ouvir, me apoiar e pelos nossos cafezinhos.A Gabriela, por sempre estar ao meu lado me dando força e apoio, pelos nossos almoços diários na copa do departamento que tornavam meu dia mais alegre e por todo carinho e amizade.A Lara, pela amizade e por todo carinho e apoio. Por ser essa pessoa tão agradável e acessível por sempre estar disposta a me ourvir. Tenho a impressão de ter sido uma criança brincando à beira-mar, divertindo-me em descobrir uma pedrinha mais lisa ou uma concha mais bonita que as outras, enquanto o imenso oceano da verdade continua misterioso diante de meus olhos". Oral squamous cell carcinoma (SCC) is a malignant tumor with high morbidity and mortality rates, and it is difficult to treat. Conventional treatment for oral SCCs includes surgery and radiotherapy that may be followed by chemotherapy. Although these treatments are widely used, they are ineffective against some resistant tumors. Isaac Newton RESUMOOncologic photodynamic therapy (PDT) has been used as an adjuvant treatment for oral SCCs, especially in less invasive cases that require tumor reduction before surgical resection. However, like conventional treatments, PDT can induce the occurrence of resistant cell populations such as cutaneous carcinomas and colon and breast adenocarcinomas. The hypothesis that oral SCCs develop resistance to PDThas not yet been tested. Therefore, the aims of this study were to investigate whether oral SCCs (SCC9) develop resistance to several cycles of 5-aminolevulinic acidmediated PDT (5-ALA-PDT) and to determine whether the expression of markers associated with cell survival (NFB, Bcl-2, iNOS, mTOR, and Akt) is altered during this process. An oral SCC (SCC9) cell line was used, which was subjected to the following conditions: 1) Control: cultured without any treatment; 2) ALA: incubated with 5-ALA (1 mM for 4 h); 3) LED: treated with LED light (630 nm, 5.86 J/cm 2 , 22.5 J, 150 mW, 150 s); and 4) PDT: treated with 5-ALA-PDT (with the protocols of the ALA and LED groups combined) generating a lethal dose of 90%. Initially, only one cycle of PDT was administered, and cell viability was determined in all groups 24, 48, 72, and 120 h after irradiation. Subsequently, the DNA fragmentation detection assay (TUNEL) and immunofluorescence analysis of the expression of proteins NFB, Bcl-2, iNOS, pmTOR, ...

show abstract

Mitochondrial and endoplasmic reticulum stress-induced apoptotic pathways are activated by 5-aminolevulinic acid-based photodynamic therapy in HL60 leukemia cells

Cited by 107 publications

References 42 publications

Bax is essential for mitochondrion-mediated apoptosis but not for cell death caused by photodynamic therapy

Bax is essential for mitochondrion-mediated apoptosis but not for cell death caused by photodynamic therapy

Intracellular signaling mechanisms in photodynamic therapy

Resistência de células de carcinoma epidermóide bucal à terapia fotodinâmica mediada pelo ácido 5-aminolevulínico

Contact Info

Product

Resources

About