Photodynamic Therapy with 5-Aminolevulinic Acid Induces Apoptosis and Caspase Activation in Malignant T Cells

2001 ◽  
Vol 5 (1) ◽  
pp. 8-13 ◽  
Author(s):  
Faten Gad ◽  
Gilles Viau ◽  
Michele Bousbira ◽  
Richard Bertrand ◽  
Robert Bissonnette
Keyword(s):  
Photodynamic Therapy ◽  
Dna Fragmentation ◽  
Caspase 3 ◽  
Aminolevulinic Acid ◽  
Light Exposure ◽  
Red Light ◽  
Jurkat Cells ◽  
Caspase Activation ◽  
Light Fluence ◽  
Malignant T Cells

Background: Preliminary studies have suggested that photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) can improve psoriasis and mycosis fungoides, two diseases where normal or malignant T cells play a central role. Objectives: To determine if ALA-PDT induces apoptosis and caspase activation in Jurkat cells, a malignant T-cell line. Methods: Jurkat cells were incubated with ALA in the presence of [14C]-thymidine followed by red light exposure. DNA fragmentation was measured 24 hours later with a DNA elution assay. The influence on DNA fragmentation of ALA concentration, time between ALA addition and light exposure, as well as light fluence were studied. The occurrence of oligonucleosome-sized DNA fragmentation was also studied with DNA electrophoresis. Caspase-3-like activity was monitored by measuring Ac-DEVD-AMC hydrolysis. Results: DNA fragmentation as high as 88% was observed 24 hours after ALA-PDT. The percentage of DNA fragmentation increased with increasing doses of ALA, red light fluence, as well as longer incubation time with ALA. DNA fragmentation was observed as early as 3 hours after ALA-PDT. The presence of apoptosis after ALA-PDT was confirmed by DNA electrophoresis. An increase in caspase-3-like activities was detected following ALA-PDT. Conclusion: ALA-PDT induces apoptosis and caspase-3-like activation in Jurkat cells.

scholarly journals TLD1433-Mediated Photodynamic Therapy with an Optical Surface Applicator in the Treatment of Lung Cancer Cells In Vitro

2020 ◽  
Vol 13 (7) ◽  
pp. 137 ◽  
Author(s):  
Sarah Chamberlain ◽  
Houston D. Cole ◽  
John Roque ◽  
David Bellnier ◽  
Sherri A. McFarland ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Photodynamic Therapy ◽  
Cell Viability ◽  
Light Propagation ◽  
Residual Disease ◽  
Red Light ◽  
Optical Surface ◽  
Light Fluence ◽  
532 Nm

Intra-operative photodynamic therapy (IO-PDT) in combination with surgery for the treatment of non-small cell lung cancer and malignant pleural mesothelioma has shown promise in improving overall survival in patients. Here, we developed a PDT platform consisting of a ruthenium-based photosensitizer (TLD1433) activated by an optical surface applicator (OSA) for the management of residual disease. Human lung adenocarcinoma (A549) cell viability was assessed after treatment with TLD1433-mediated PDT illuminated with either 532- or 630-nm light with a micro-lens laser fiber. This TLD1433-mediated PDT induced an EC50 of 1.98 μM (J/cm2) and 4807 μM (J/cm2) for green and red light, respectively. Cells were then treated with 10 µM TLD1433 in a 96-well plate with the OSA using two 2-cm radial diffusers, each transmitted 532 nm light at 50 mW/cm for 278 s. Monte Carlo simulations of the surface light propagation from the OSA computed light fluence (J/cm2) and irradiance (mW/cm2) distribution. In regions where 100% loss in cell viability was measured, the simulations suggest that >20 J/cm2 of 532 nm was delivered. Our studies indicate that TLD1433-mediated PDT with the OSA and light simulations have the potential to become a platform for treatment planning for IO-PDT.

4-hydroxynonenal induces a cellular redox status-related activation of the caspase cascade for apoptotic cell death

2000 ◽  
Vol 113 (4) ◽  
pp. 635-641 ◽  
Author(s):  
W. Liu ◽  
M. Kato ◽  
A.A. Akhand ◽  
A. Hayakawa ◽  
H. Suzuki ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Dna Fragmentation ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
K562 Cells ◽  
Apoptotic Cell Death ◽  
Jurkat Cells ◽  
Substrate Peptide ◽  
Caspase Cascade

4-Hydroxynonenal (HNE), a diffusible product of lipid peroxidation, has been suggested to be a key mediator of oxidative stress-induced cell death. In this study, we partially characterized the mechanism of HNE-mediated cytotoxicity. Incubation of human T lymphoma Jurkat cells with 20–50 μM HNE led to cell death accompanied by DNA fragmentation. Western blot analysis showed that HNE-treatment induced time- and dose-dependent activation of caspase-8, caspase-9 and caspase-3. HNE-induced caspase-3 processing was confirmed by a flow cytometric demonstration of increased catalytic activity on the substrate peptide. HNE treatment also led to remarkable cleavage of poly(ADP-ribose) polymerase (PARP), which was prevented by pretreatment of cells with DEVD-FMK as a caspase-3 inhibitor. The HNE-mediated activation of caspases, cleavage of PARP and DNA fragmentation were blocked by antioxidants cysteine, N-acety-L-cysteine and dithiothreitol, but not by two other HNE-reactive amino acids lysine and histidine, or by cystine, the oxidized form of cysteine. HNE rapidly decreased levels of intracellular reduced glutathione (GSH) and its oxidized form GSSG, and these were also attenuated by the reductants. Coincubation of Jurkat cells with a blocking anti-Fas antibody prevented Fas-induced but not HNE-induced activation of caspase-3. HNE also activated caspase-3 in K562 cells that do not express functional Fas. Our results thereby demonstrate that HNE triggers oxidative stress-linked apoptotic cell death through activation of the caspase cascade. The results also suggest a possible mechanism involving a direct scavenge of intracellular GSH by HNE.

Preferential Induction of B Cell Apoptosis Using Photodynamic Therapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4643-4643
Author(s):  
Gorazd Krosl ◽  
Pascale Dube ◽  
Nancy Dallaire ◽  
Marc Vaillancourt ◽  
Denis-Claude Roy
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Photodynamic Therapy ◽  
B Cells ◽  
T Lymphocytes ◽  
B Cell ◽  
Dna Fragmentation ◽  
Caspase 3 ◽  
Induction Of Apoptosis ◽  
B Lineage

Abstract Apoptotic cell death in cancer cells promotes antigen presentation and favors the development of an anti-tumor vaccination effect. While lymphoma cells can easily be obtained from lymph nodes or peripheral blood, these malignant cells usually co-localize with normal hematopoietic T lymphocytes, rendering the selective induction of apoptosis in malignant B cells particularly difficult. We have found that photodynamic therapy (PDT) using the photosensitizer 4–5 dibromorhodamine methyl ester (TH9402) and visible light (514 nm) can be used to preferentially eliminate malignant B-lineage non-Hodgkin’s lymphoma cells (mean of 3–4 logs) over T lymphocytes. As a rhodamine derivative, TH9402 cellular efflux is mediated through the P-glycoprotein (Pgp) pump. However, the preferential elimination of B cells over resting T cells could not be ascribed to Pgp inactivation and we found no difference in intracellular retention of TH9402 between B and T cells. In order to understand the molecular events leading to such high B cell susceptibility to PDT, we then investigated the nature of death pathways involved. To determine whether apoptosis was the preponderant mechanism leading to the rapid elimination of B cells, we measured the binding of Annexin V (AnnV) in 7-aminoactinomycin D (7AAD) negative (i.e. live) B and T cells using flow cytometry, and quantified DNA fragmentation and caspase 3 and 9 activity in isolated CD3+ and CD19+ PDT treated and untreated cells. We found that B cells demonstrated high levels of apoptosis after PDT, with 53±1.3% (mean±SE) AnnexinV+/7AAD- cells compared to 30±1.9% in T cells (p< 0.05). The extent of DNA fragmentation, as determined by the TUNEL reaction, was extensive in B cells (33.7±9.8%)(mean±SE) but not T cells (2.3±0.1%) when measured at 4 hours post PDT (p<0.01). After PDT, catalytic caspase 3 levels were also 4-fold higher in CD19+ cells than CD3+ cells (p<0.01). In contrast, caspase 9 levels remained low for both cell types. The induction of apoptosis translated into the elimination of more than 90% of B cells within 4 hours after PDT, while the majority of T cells were not affected. Importantly, similar elimination of B-lineage cell lines and patient cells was observed, using a limiting dilution assay, whether cells overexpressed the anti-apoptotic bcl-2 protein or not. Thus, these results indicate that the predominant caspase 3 apoptotic pathway is specifically implicated in PDT-induced B cell death, and its early activation explains the rapid and profound sensitivity of B lymphocytes to PDT. This strategy could promote tumor cell vaccination in the context of autologous TH9402-purged stem cell transplantation for patients with B-lineage malignancies. In addition, preferential B cell targeting could take advantage of the crucial immunomodulatory role of apoptosis for the treatment of patients with autoimmune B cell disorders.

CO2 LASER PLUS PHOTODYNAMIC THERAPY VERSUS CO2 LASER IN THE TREATMENT OF CONDYLOMA ACUMINATUM: A RANDOMIZED COMPARATIVE STUDY

2012 ◽  
Vol 05 (01) ◽  
pp. 1150008 ◽  
Author(s):  
HUIFENG LIU ◽  
PING ZHANG ◽  
XIANGJIE AN ◽  
LIU YANG ◽  
YAN LI ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Adverse Effects ◽  
Co2 Laser ◽  
Aminolevulinic Acid ◽  
Complete Response Rate ◽  
Red Light ◽  
Complete Response ◽  
Condyloma Acuminatum ◽  
Recurrence Rates ◽  
Laser Group

To compare the efficacy and safety of CO2 laser plus 5-aminolevulinic acid (ALA) photodynamic therapy (PDT) with CO2 laser for the treatment of multiple condyloma acuminatum (CA), 120 patients with multiple CA were allocated into two groups — combined group ( CO2 laser plus ALA-PDT, n = 60) and CO2 laser group ( CO2 laser plus placebo-PDT, n = 60). After CO2 laser, a 20% ALA or a placebo solution was applied to the CA area 3 h before illumination with red light (635 nm, 100 mW/cm2, 80 J/cm2). The treatment was repeated seven days after the first treatment if the lesions were not completely resolved. The complete response rate, recurrence rate and adverse effects in the two groups were analyzed. After two treatments, the complete response rates in the CO2 laser group and combined group were 100% (509/509) and 100% (507/507) in the CA (p > 0.05), respectively. The recurrence rates in the CO2 laser group and combined group were 44.9% (229/509) and 10.6% (54/507) in the CA (p < 0.05), respectively. The adverse effects in CO2 laser group was more than that in combined group. The combined group is a more effective treatment for multiple CA compared with CO2 laser group. T/S. Style the highlighted text as abstract.

Photodynamic Therapy for Head and Neck Cancer Xenografts in Athymic Mice

1986 ◽  
Vol 95 (5) ◽  
pp. 602-606 ◽  
Author(s):  
James H. Hill ◽  
Randall L. Plant ◽  
David M. Harris ◽  
Randal C. Paniello
Keyword(s):  
Photodynamic Therapy ◽  
Light Intensity ◽  
Head And Neck ◽  
Treatment Time ◽  
Light Exposure ◽  
Red Light ◽  
Human Head ◽  
Athymic Mice ◽  
Squamous Cancer ◽  
Argon Dye Laser

This study examines efficacy and optimal treatment variables of photodynamic therapy (PDT) for human head and neck squamous cancer (HNSC) xenografts in athymic mice. Two and four days after injection of hematoporphyrin derivative (HPD), tumors were illuminated with red light from an argon-dye laser. Sixty-three tumors were treated. With HPD dose and light intensity constant at 7.5 mg/kg and 100 mW/cm2, respectively, the extent of tumor necrosis was strongly dependent on duration of light exposure. There was no substantial difference in results for 30- and 60-minute treatment durations between animals injected with HPD 2 and 4 days before treatment. After 30 minutes treatment time, responses were seen in 8 of 10 mice (2 days post-HPD) and 11 of 12 mice (4 days post-HPD). After 60 minutes treatment time, toxicity was high. We conclude that, in this model, PDT is effective in selective killing of HNSC. For future comparison studies in this model, if the indicated HPD dose and light intensity are used we recommend a 2-day delay after HPD injection and a light exposure duration of 30 minutes

scholarly journals Continuous Low-Irradiance Photodynamic Therapy: A New Therapeutic Paradigm

2012 ◽  
Vol 10 (Suppl_2) ◽  
pp. S-14-S-17 ◽  
Author(s):  
Gary S. Rogers
Keyword(s):  
Photodynamic Therapy ◽  
Light Exposure ◽  
Light Therapy ◽  
Principal Factor ◽  
Tumor Control ◽  
Fluence Rate ◽  
Energy Delivery ◽  
Light Fluence ◽  
Home Based ◽  
Home Based Therapy

A principal factor in determining the biologic consequences of photodynamic therapy (PDT) is the light fluence rate. Preclinical and, more recently, clinical studies have focused on low-irradiance schemes, suggesting that prolonged light exposure, better known as CLIPT (continuous low-irradiance PDT), may improve tumor control while reducing morbidity. After a brief look at the origin of light therapy and photosensitizers, this article turns to the promising animal research supporting the use of low- and ultra-low fluence rate PDT, which serves as the basis of the ongoing CLIPT dosimetry trials for patients with chest wall progression of breast cancer. The future of CLIPT seems to be a home-based therapy using a portable, self-contained energy delivery system.

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