In situ production of ROS in the skin by photodynamic therapy as a powerful tool in clinical dermatology

Fonda‐Pascual, Pablo; Moreno‐Arrones, Óscar M.; Alegre-Sánchez, A.; Saceda‐Corralo, David; Buendía-Castaño, Diego; Pindado‐­Ortega, Cristina; Fernández-González, Pablo; Velázquez-Kennedy, Kyra; Calvo-Sánchez, María I.; Harto-Castaño, Antonio; Pérez‐García, B.; Bagazgoitia, Lorea; Vañó‐Galván, Sergio; Espada, Jesús; Jaén‐Olasolo, Pedro

doi:10.1016/j.ymeth.2016.07.008

Cited by 43 publications

(25 citation statements)

References 130 publications

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“…The major effect of photodynamic therapy (PDT) in acne is the generation of ROS [ 71 , 72 ]. Thus, PDT mimics the effects of BPO-mediated upregulation of p53.…”

Section: Peroxides and Photodynamic Therapymentioning

confidence: 99%

p53: key conductor of all anti-acne therapies

Melnik

2017

J Transl Med

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This review based on translational research predicts that the transcription factor p53 is the key effector of all anti-acne therapies. All-trans retinoic acid (ATRA) and isotretinoin (13-cis retinoic acid) enhance p53 expression. Tetracyclines and macrolides via inhibiting p450 enzymes attenuate ATRA degradation, thereby increase p53. Benzoyl peroxide and hydrogen peroxide elicit oxidative stress, which upregulates p53. Azelaic acid leads to mitochondrial damage associated with increased release of reactive oxygen species inducing p53. p53 inhibits the expression of androgen receptor and IGF-1 receptor, and induces the expression of IGF binding protein 3. p53 induces FoxO1, FoxO3, p21 and sestrin 1, sestrin 2, and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), the key inducer of isotretinoin-mediated sebocyte apoptosis explaining isotretinoin’s sebum-suppressive effect. Anti-androgens attenuate the expression of miRNA-125b, a key negative regulator of p53. It can thus be concluded that all anti-acne therapies have a common mode of action, i.e., upregulation of the guardian of the genome p53. Immortalized p53-inactivated sebocyte cultures are unfortunate models for studying acne pathogenesis and treatment.

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“…The major effect of photodynamic therapy (PDT) in acne is the generation of ROS [ 71 , 72 ]. Thus, PDT mimics the effects of BPO-mediated upregulation of p53.…”

Section: Peroxides and Photodynamic Therapymentioning

confidence: 99%

p53: key conductor of all anti-acne therapies

Melnik

2017

J Transl Med

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“…None of them are individually toxic, but their combination triggers the photodynamic reaction which is tumor ablative by generating highly reactive oxygen species (ROS), mainly singlet oxygen ( 1 O 2 ) [6]. These molecules have short half-life and a destruction radius in the range of nanometers, being, therefore, the main targets the organelles where PSs are located [7,8]. The activation of the PS is obtained by irradiating with light of appropriate wavelength, generally in the red region of the visible spectrum (620–690 nm); with high capacity to deeply penetrate into the tissues [9].…”

Section: Introductionmentioning

confidence: 99%

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

Mascaraque

Delgado-Wicke

Damián

et al. 2019

IJMS

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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.

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“…After absorbing energy from the light, the photosensitizer moves into higher energetic states and transfers this additional energy to molecular oxygen directly or indirectly via type II or type I photochemical reactions, respectively . These reactions form reactive oxygen species (ROS), which then damage cellular components like proteins, lipids, and DNA or indeed the photosensitizer itself, inducing photobleaching . The cellular cascades of ROS thus generated, overwhelm the cell's inherent antioxidant defense and ultimately lead to cell death via apoptosis and necrosis, or alternatively, a destructive form of autophagy .…”

Section: Introductionmentioning

confidence: 99%

An experimental investigation of a novel iron chelating protoporphyrin IX prodrug for the enhancement of photodynamic therapy

et al. 2018

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ObjectivesNon‐melanoma skin cancers are the most frequently occurring type of cancer worldwide. They can be effectively treated using topical dermatological photodynamic therapy (PDT) employing protoporphyrin IX (PpIX) as the active photosensitising agent as long as the disease remains superficial. Novel iron chelating agents are being investigated to enhance the effectiveness and extend the applications of this treatment modality, as limiting free iron increases the accumulation of PpIX available for light activation and thus cell kill.MethodsHuman lung fibroblasts (MRC‐5) and epithelial squamous carcinoma (A431) cells were treated with PpIX precursors (aminolaevulinic acid [ALA] or methyl‐aminolevulinate [MAL]) with or without the separate hydroxypyridinone iron chelating agent (CP94) or alternatively, the new combined iron chelator and PpIX producing agent, AP2‐18. PpIX fluorescence was monitored hourly for 6 hours prior to irradiation. PDT effectiveness was then assessed the following day using the lactate dehydrogenase and neutral red assays.ResultsGenerally, iron chelation achieved via CP94 or AP2‐18 administration significantly increased PpIX fluorescence. ALA was more effective as a PpIX‐prodrug than MAL in A431 cells, corresponding with the lower PpIX accumulation observed with the latter congener in this cell type. Addition of either iron chelating agent consistently increased PpIX accumulation but did not always convey an extra beneficial effect on PpIX‐PDT cell kill when using the already highly effective higher dose of ALA. However, these adjuvants were highly beneficial in the skin cancer cells when compared with MAL administration alone. AP2‐18 was also at least as effective as CP94 + ALA/MAL co‐administration throughout and significantly better than CP94 supplementation at increasing PpIX fluorescence in MRC5 cells as well as at lower doses where PpIX accumulation was observed to be more limited.ConclusionsPpIX fluorescence levels, as well as PDT cell kill effects on irradiation can be significantly increased by pyridinone iron chelation, either via the addition of CP94 to the administration of a PpIX precursor or alternatively via the newly synthesized combined PpIX prodrug and siderophore, AP2‐18. The effect of the latter compound appears to be at least equivalent to, if not better than, the separate administration of its constituent parts, particularly when employing MAL to destroy skin cancer cells. AP2‐18 therefore warrants further detailed analysis, as it may have the potential to improve dermatological PDT outcomes in applications currently requiring enhancement. Lasers Surg. Med. 50:552–565, 2018. © 2018 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

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In situ production of ROS in the skin by photodynamic therapy as a powerful tool in clinical dermatology

Cited by 43 publications

References 130 publications

p53: key conductor of all anti-acne therapies

p53: key conductor of all anti-acne therapies

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

An experimental investigation of a novel iron chelating protoporphyrin IX prodrug for the enhancement of photodynamic therapy

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