scholarly journals Mitotic Catastrophe Induced in HeLa Tumor Cells by Photodynamic Therapy with Methyl-aminolevulinate

2019 ◽  
Vol 20 (5) ◽  
pp. 1229 ◽  
Author(s):  
Marta Mascaraque ◽  
Pablo Delgado-Wicke ◽  
Alejandra Damian ◽  
Silvia Lucena ◽  
Elisa Carrasco ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Tumor Cells ◽  
Protoporphyrin Ix ◽  
Aurora Kinase ◽  
Mitotic Catastrophe ◽  
Mitotic Apparatus ◽  
Human Carcinoma ◽  
Cancer Cell Death ◽  
Multipolar Spindles ◽  
Methyl Aminolevulinate

Photodynamic therapy (PDT) constitutes a cancer treatment modality based on the administration of a photosensitizer, which accumulates in tumor cells. The subsequent irradiation of the tumoral area triggers the formation of reactive oxygen species responsible for cancer cell death. One of the compounds approved in clinical practice is methyl-aminolevulinate (MAL), a protoporphyrin IX (PpIX) precursor intermediate of heme synthesis. We have identified the mitotic catastrophe (MC) process after MAL-PDT in HeLa human carcinoma cells. The fluorescence microscopy revealed that PpIX was located mainly at plasma membrane and lysosomes of HeLa cells, although some fluorescence was also detected at endoplasmic reticulum and Golgi apparatus. Cell blockage at metaphase-anaphase transition was observed 24 h after PDT by phase contrast microscopy and flow cytometry. Mitotic apparatus components evaluation by immunofluorescence and Western blot indicated: multipolar spindles and disorganized chromosomes in the equatorial plate accompanied with dispersion of centromeres and alterations in aurora kinase proteins. The mitotic blockage induced by MAL-PDT resembled that induced by two compounds used in chemotherapy, taxol and nocodazole, both targeting microtubules. The alterations in tumoral cells provided evidence of MC induced by MAL-PDT, resolving mainly by apoptosis, directly or through the formation of multinucleate cells.

scholarly journals Alectinib Treatment Improves Photodynamic Therapy in Cancer Cell Lines of Different Origin

2020 ◽  
Author(s):  
Bernhard Gillissen ◽  
Antje Richter ◽  
Wolfgang Kemmner
Keyword(s):  
Photodynamic Therapy ◽  
Tumor Cells ◽  
Cell Lines ◽  
Flow Cytometric Analysis ◽  
Protoporphyrin Ix ◽  
Annexin V ◽  
Cancer Drug ◽  
Selective Treatment ◽  
Anaplastic Lymphoma ◽  
Different Origin

Abstract Background: Photodynamic therapy with a photosensitizer such as protoporphyrin-IX, a light sensitive metabolite of heme synthesis, is a highly selective treatment for various carcinomas. In previous studies, we found a significant down regulation of the relevant enzyme ferrochelatase in gastrointestinal carcinomas leading to an accumulation of protoporphyrin-IX within the tumor cells. Recent studies showed that a novel anti-cancer drug, Alectinib, an orally available, highly selective, potent second-generation inhibitor of anaplastic lymphoma tyrosinkinase binds to ferrochelatase. Therefore, we were interested to see whether Alectinib treatment might lead to an accumulation of protoporphyrin IX. Methods : Tumor cells of different origin were cultured, treated with LED-light and Alectinib. Results were gained by flow cytochemistry, immunohistochemistry and western blotting. Apoptosis was determined by flow cytometric analysis of Annexin V-FITC stained cells. In addition, cells were counterstained with propidium iodide (PI) to distinguish early apoptotic cells (Annexin V-positive/PI-negative) and late apoptosis/necroptotic cells.Results: Here, we report that photodynamic treatment of tumor cell lines of different origin in combination with Alectinib increased protoporphyrin-IX specific fluorescence and concomitantly cell death. Conclusions: The usage of Alectinib might be a crucial step for enhancing the effectiveness of photodynamic therapy. Further experiments will show whether photodynamic therapy in combination with Alectinib could be a new strategy for the treatment of e.g. peritoneal disseminated carcinomas.

scholarly journals Regression Analysis of Protoporphyrin IX Measurements Obtained During Dermatological Photodynamic Therapy

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 72 ◽  
Author(s):  
Jessica Tyrrell ◽  
Cheryl Paterson ◽  
Alison Curnow
Keyword(s):  
Photodynamic Therapy ◽  
Clinical Outcome ◽  
Imaging System ◽  
Protoporphyrin Ix ◽  
Air Cooling ◽  
Non Invasive ◽  
Fold Reduction ◽  
Methyl Aminolevulinate ◽  
Superficial Basal Cell Carcinoma ◽  
Hands And Feet

Photodynamic therapy (PDT) is a light activated drug therapy that can be used to treat a number of dermatological cancers and precancers. Improvement of efficacy is required to widen its application. Clinical protoporphyrin IX (PpIX) fluorescence data were obtained using a pre-validated, non-invasive imaging system during routine methyl aminolevulinate (MAL)-PDT treatment of 172 patients with licensed dermatological indications (37.2% actinic keratosis, 27.3% superficial basal cell carcinoma and 35.5% Bowen’s disease). Linear and logistic regressions were employed to model any relationships between variables that may have affected PpIX accumulation and/or PpIX photobleaching during irradiation and thus clinical outcome at three months. Patient age was found to be associated with lower PpIX accumulation/photobleaching, however only a reduction in PpIX photobleaching appeared to consistently adversely affect treatment efficacy. Clinical clearance was reduced in lesions located on the limbs, hands and feet with lower PpIX accumulation and subsequent photobleaching adversely affecting the outcome achieved. If air cooling pain relief was employed during light irradiation, PpIX photobleaching was lower and this resulted in an approximate three-fold reduction in the likelihood of achieving clinical clearance. PpIX photobleaching during the first treatment was concluded to be an excellent predictor of clinical outcome across all lesion types.

scholarly journals Design and synthesis of 5-aminolaevulinic acid/3-hydroxypyridinone conjugates for photodynamic therapy: enhancement of protoporphyrin IX production and photo-toxicity in tumor cells

MedChemComm ◽  
2016 ◽  
Vol 7 (6) ◽  
pp. 1190-1196 ◽  
Author(s):  
Tao Zhou ◽  
Le-Le Shao ◽  
Sinan Battah ◽  
Chun-Feng Zhu ◽  
Robert C. Hider ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Tumor Cells ◽  
Protoporphyrin Ix ◽  
Design And Synthesis ◽  
Aminolaevulinic Acid

A series of ALA-HPO conjugates was prepared. One such conjugate was found to possess high phototoxicity.

scholarly journals Alectinib treatment improves photodynamic therapy in cancer cell lines of different origin

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bernhard Gillissen ◽  
Antje Richter ◽  
Frank Essmann ◽  
Wolfgang Kemmner
Keyword(s):  
Photodynamic Therapy ◽  
Tumor Cells ◽  
Cell Lines ◽  
Flow Cytometric Analysis ◽  
Protoporphyrin Ix ◽  
Cancer Drug ◽  
Photodynamic Treatment ◽  
Selective Treatment ◽  
Anaplastic Lymphoma ◽  
Different Origin

Abstract Background Photodynamic therapy with a photosensitizer such as protoporphyrin-IX, a light sensitive metabolite of heme synthesis, is a highly selective treatment for various carcinomas. In previous studies, we found a significant down regulation of the relevant enzyme ferrochelatase in gastrointestinal carcinomas leading to an accumulation of protoporphyrin-IX within the tumor cells. Recent studies showed that a novel anti-cancer drug, Alectinib, an orally available, highly selective, potent second-generation inhibitor of anaplastic lymphoma tyrosinkinase binds to ferrochelatase. Therefore, we were interested to see whether Alectinib treatment might lead to an accumulation of protoporphyrin IX. Methods Tumor cells of different origin were cultured, treated with LED-light and Alectinib. Results were gained by flow cytometry, immunohistochemistry and western blotting. Apoptosis was determined by flow cytometric analysis of Annexin V-FITC stained cells. In addition, cells were counterstained with propidium iodide to distinguish early apoptotic cells and late apoptotic/necrotic cells. Results Here, we report that photodynamic treatment of tumor cell lines of different origin in combination with Alectinib increased protoporphyrin-IX specific fluorescence and concomitantly cell death. Conclusions The usage of Alectinib could be another step for enhancing the effectiveness of photodynamic therapy. Further experiments will show whether photodynamic therapy in combination with Alectinib could be a new strategy for the treatment of e.g. peritoneal disseminated carcinomas.

scholarly journals How Much Protoporphyrin IX Must Be Activated to Obtain Full Efficacy of Methyl Aminolevulinate Photodynamic Therapy? Implication for Treatment Modifications

2021 ◽  
Vol 14 (4) ◽  
pp. 333
Author(s):  
Hans Christian Wulf ◽  
Ida M. Heerfordt ◽  
Peter Alshede Philipsen
Keyword(s):  
Photodynamic Therapy ◽  
Red Light ◽  
Protoporphyrin Ix ◽  
Treatment Modalities ◽  
Light Illumination ◽  
Cure Rate ◽  
Illumination Time ◽  
Full Effect ◽  
Methyl Aminolevulinate ◽  
Cure Rates

Photodynamic therapy (PDT) with methyl aminolevulinate (MAL) is a popular treatment for actinic keratoses (AK), and several PDT treatment modalities with similar cure rates are in use. The effect relies on the activation of protoporphyrin IX (PpIX) in premalignant cells. This study aimed to measure PpIX during each treatment modality to determine the minimal PpIX activation and shortest exposure time for optimal cure rate. In four different treatment modalities, we established the PpIX formation up to three hours after MAL application without illumination and measured the speed of PpIX photoactivation during 9 min of red light (37 J/cm2). The level of PpIX three hours after MAL application was set to 100 PpIX units. In comparison, 85 PpIX units were formed during daylight PDT, 57 PpIX units during pulse PDT, and 52 PpIX units without any curettage prior to MAL. The activation of 50 PpIX units should, therefore, be enough to obtain a full effect on AK. Further, red light illumination may be shortened from 9 min to 1–2 min. The results indicate that PDT can be performed successfully with half the illumination time used in daylight PDT today and with one fourth of the illumination time used in classical PDT.

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