Effects of hypericin and a chlorin based photosensitizer alone or in combination in squamous cell carcinoma cells in the dark

Gyenge, Emina Bešić; Forny, Patrick; Lüscher, Daniel; Laass, Andrea; Walt, Heinrich; Maake, Caroline

doi:10.1016/j.pdpdt.2012.03.006

Cited by 28 publications

(21 citation statements)

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“…Photosensitizers (PSs) used in PDT are usually administered systemically and show a preferential accumulation in malignant cells. Nevertheless, exposure of healthy non-malignant cells to PS remains potentially high, especially in the vasculature [4]. Tumor response to PDT is variable, ranging from high sensitivity to extreme resistance.…”

Section: Introductionmentioning

confidence: 99%

“…The PS Hyp has been claimed to display a minimal dark (light-independent) cytotoxicity [6,7,9], however, recently it was shown that Hyp had light-independent cytotoxic effects in a wide range of concentrations in various cell types [4,21,22]. The Hyp light-independent effects could be due to various mechanism, for example reduction of intracellular pH, or due to inhibition of different enzymes [4,23,24,25].…”

Section: Introductionmentioning

confidence: 99%

“…The Hyp light-independent effects could be due to various mechanism, for example reduction of intracellular pH, or due to inhibition of different enzymes [4,23,24,25]. There is also possibility that multiple mechanisms are running simultaneously, due to Hyp interaction with different molecules at the Hyp accumulation sites such as mitochondria, ER and GA. …”

Section: Introductionmentioning

confidence: 99%

“…Up to this date, findings regarding Hyp light-independent effects are as follows. (I) Hyp colocalizes with PKCα in U87 MG cells, and Hyp binding assays and molecular modeling indicate direct interactions between Hyp and PKCα [26,27]; (II) in U87 MG cells, the majority of phosphorylated Bcl2 co-localizes with PKCα [25]; (III) Hyp in the dark follows the ceramide pathway, translocates, and increases PKCδ autophosphorylation at Ser645 in the GA and nucleus of U87 MG cells [28]; (IV) Hyp affects distribution of pro-apoptotic proteins Bak and Bax, and anti-apoptotic Bcl2 in human glioma U87 MG and endothelial HCAEC cells [29,30]; (V) Hyp affects cell viability in metabolically distinct cell phenotypes differently [4,21,22,25,30]. In addition, our newest work suggests that Hyp causes the light-independent effects in bioenergetics, increases oxidative stress, and results in adaptive changes in ultrastructure.…”

Section: Introductionmentioning

confidence: 99%

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Hypericin in the Dark: Foe or Ally in Photodynamic Therapy?

Huntošová

Štroffeková

2016

Cancers

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Photosensitizers (PSs) in photodynamic therapy (PDT) are, in most cases, administered systemically with preferential accumulation in malignant tissues; however, exposure of non-malignant tissues to PS may also be clinically relevant, when PS molecules affect the pro-apoptotic cascade without illumination. Hypericin (Hyp) as PS and its derivatives have long been studied, regarding their photodynamic and photocytotoxic characteristics. Hyp and its derivatives have displayed light-activated antiproliferative and cytotoxic effects in many tumor cell lines without cytotoxicity in the dark. However, light-independent effects of Hyp have emerged. Contrary to the acclaimed Hyp minimal dark cytotoxicity and preferential accumulation in tumor cells, it was recently been shown that non-malignant and malignant cells uptake Hyp at a similar level. In addition, Hyp has displayed light-independent toxicity and anti-proliferative effects in a wide range of concentrations. There are multiple mechanisms underlying Hyp light-independent effects, and we are still missing many details about them. In this paper, we focus on Hyp light-independent effects at several sub-cellular levels—protein distribution and synthesis, organelle ultrastructure and function, and Hyp light-independent effects regarding reactive oxygen species (ROS). We summarize work from our laboratories and that of others to reveal an intricate network of the Hyp light-independent effects. We propose a schematic model of pro- and anti-apoptotic protein dynamics between cell organelles due to Hyp presence without illumination. Based on our model, Hyp can be explored as an adjuvant therapeutic drug in combination with chemo- or radiation cancer therapy.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hypericin in the Dark: Foe or Ally in Photodynamic Therapy?

Huntošová

Štroffeková

2016

Cancers

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“…6 The dark toxicity of a mixture of hypericin and Foslipos® (1:1) was studied on two different head and neck squamous cell carcinoma cell lines. 7 The obtained data suggested that this combination decreases the dark toxicity effect. Nevertheless, cell viability differences between each PS alone and the mixture were not biologically significant on UMB-SCC 745 and 969 under these conditions.…”

Section: Introductionmentioning

confidence: 88%

Improved photodynamic effect through encapsulation of two photosensitizers in lipid nanocapsules

et al. 2018

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Efficacy and Safety of Topical Hypericin Photodynamic Therapy for Early-Stage Cutaneous T-Cell Lymphoma (Mycosis Fungoides)

et al. 2022

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ImportanceGiven that mycosis fungoides−cutaneous T-cell lymphoma (MF/CTCL) is chronic, there is a need for additional therapies with minimal short- and long-term adverse effects. Topical synthetic hypericin ointment, 0.25%, activated with visible light is a novel, nonmutagenic photodynamic therapy (PDT).ObjectivesTo determine the efficacy and safety of topical synthetic hypericin ointment, 0.25%, activated with visible light as a nonmutagenic PDT in early-stage MF/CTCL.Design, Settings, and ParticipantsThis was a multicenter, placebo-controlled, double-blinded, phase 3 randomized clinical trial (FLASH study) conducted from December 2015 to November 2020 at 39 academic and community-based US medical centers. Participants were adults (≥18 years) with early-stage (IA-IIA) MF/CTCL.InterventionsIn cycle 1, patients were randomized 2:1 to receive hypericin or placebo to 3 index lesions twice weekly for 6 weeks. In cycle 2, all patients received the active drug for 6 weeks to index lesions. In cycle 3 (optional), both index and additional lesions received active drug for 6 weeks.Main Outcomes and MeasuresThe primary end point was index lesion response rate (ILRR), defined as 50% or greater improvement in modified Composite Assessment of Index Lesion Severity (mCAILS) score from baseline after 6 weeks of therapy for cycle 1. For cycles 2 and 3, open label response rates were secondary end points. Adverse events (AEs) were assessed at each treatment visit, after each cycle, and then monthly for 6 months. Data analyses were performed on December 21, 2020.ResultsThe study population comprised 169 patients (mean [SD] age, 58.4 [16.0] years; 96 [57.8%] men; 120 [72.3%] White individuals) with early-stage MF/CTCL. After 6 weeks of treatment, hypericin PDT was more effective than placebo (cycle 1 ILRR, 16% vs 4%; P = .04). The ILRR increased to 40% in patients who received 2 cycles of hypericin PDT (P < .001 vs cycle 1 hypericin) and to 49% after 3 cycles (P < .001 vs cycle 1 hypericin). Significant clinical responses were observed in both patch and plaque type lesions and were similar regardless of age, sex, race, stage IA vs IB, time since diagnosis, and number of prior therapies. The most common treatment-related AEs were mild local skin (13.5%-17.3% across cycles 1-3 vs 10.5% for placebo in cycle 1) and application-site reactions (3.2%-6.9% across cycles 1-3 vs 4% for placebo in cycle 1). No drug-related serious AEs occurred.Conclusion and RelevanceThe findings of this randomized clinical trial indicate that synthetic hypericin PDT is effective in early-stage patch and plaque MF/CTCL and has a favorable safety profile.Trial RegistrationClinicalTrials.gov Identifier: NCT02448381

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Effects of hypericin and a chlorin based photosensitizer alone or in combination in squamous cell carcinoma cells in the dark

Cited by 28 publications

References 28 publications

Hypericin in the Dark: Foe or Ally in Photodynamic Therapy?

Hypericin in the Dark: Foe or Ally in Photodynamic Therapy?

Improved photodynamic effect through encapsulation of two photosensitizers in lipid nanocapsules

Efficacy and Safety of Topical Hypericin Photodynamic Therapy for Early-Stage Cutaneous T-Cell Lymphoma (Mycosis Fungoides)

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