Necrosis predominates in the cell death of human colon adenocarcinoma HT-29 cells treated under variable conditions of photodynamic therapy with hypericin

Mikeš, Jaromír; Kleban, Ján; Sačková, Veronika; Horváth, Viktor; Jamborová, Erika; Vaculová, Alena Hyršlová; Kozubı́k, Alois; Hofmanová, Jiřina; Fedoročko, Peter

doi:10.1039/b700350a

Cited by 46 publications

(39 citation statements)

References 40 publications

(46 reference statements)

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“…In HT-29 cells, the increase in floating cells were significant in HYP groups compared to the control group for both incubation times. Our results are consistent with the work of Mikeš et al (2007) in which floating cells were increased depending on the HYP concentration and incubation time in HT-29 cells. In Caco-2 cells, increase in the number of floating cells was statistically significant in 0.04, 0.08 and 0.15 lM HYP groups compared to control group after 16 h after PDT (Table 1).…”

Section: Resultssupporting

confidence: 93%

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Alterations in dysadherin expression and F-actin reorganization: a possible mechanism of hypericin-mediated photodynamic therapy in colon adenocarcinoma cells

2014

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Dysadherin is a recently found anti-adhesion molecule, therefore detection and down regulation of its expression is promising in cancer treatment. The up-regulation of dysadherin contributes to colon cancer recurrence and metastasis. Dysadherin also has connections with cytoskeletal proteins and it can cause alterations in the organisation of filamentous actin (Factin) in metastatic cancers. In this study, hypericin (HYP)-mediated photodynamic therapy (PDT) was performed in two different grade colon adenocarcinoma cell lines HT-29 (Grade I) and Caco-2 (Grade II). Cells were treated with 0.04, 0.08 or 0.15 lM HYP concentrations and irradiated with (4 J/cm 2 ) fluorescent lamps. The effects of HYP was examined 16 and 24 h after the activation. We investigated for the first time the effect of HYP-mediated PDT on the expression of dysadherin and F-actin organisation. According to the results, HYP mediated PDT caused a decrease in gene expression and immunofluorescence staining of dysadherin and an increase in actin stress fibers and actin aggregates in HT-29 and Caco-2 cell lines. Besides, cytotoxicity, number of floating cells and apoptotic index changed depending on the cell type, HYP concentration and incubation time. We have demonstrated for the first time that dysadherin and F-actin could be target molecules for HYP-

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Section: Resultssupporting

confidence: 93%

“…Nevertheless, there are still question marks limiting its clinical use (Paszkoa et al 2011). Depending on the HYP concentration, light dose, incubation time and cell origin, the type of cell death induced by PDT can be altered (Mikeš et al 2007). …”

Section: Introductionmentioning

confidence: 99%

Alterations in dysadherin expression and F-actin reorganization: a possible mechanism of hypericin-mediated photodynamic therapy in colon adenocarcinoma cells

2014

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“…For instance, photodynamic therapy (PDT), which is the treatment of cells with a photosensitizer followed by irradiation, triggers necrosis. 160, 161 Indeed, it has been shown that treatment with the photosensitizer hypericin in combination with UV irradiation induces necrotic cell death in colon adenocarcinoma HT-29 cells 162 and melanosome-containing cells. 163 Recently, it was demonstrated that the presence or absence of RIPK3 determines the cell death modality by PDT.…”

Section: Phyisco-chemical Stress-induced Necrosismentioning

confidence: 99%

Many stimuli pull the necrotic trigger, an overview

2011

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The lab of Jürg Tschopp was the first to report on the crucial role of receptor-interacting protein kinase 1 (RIPK1) in caspase-independent cell death. Because of this pioneer finding, regulated necrosis and in particular RIPK1/RIPK3 kinase-mediated necrosis, referred to as necroptosis, has become an intensively studied form of regulated cell death. Although necrosis was identified initially as a backup cell death program when apoptosis is blocked, it is now recognized as a cellular defense mechanism against viral infections and as being critically involved in ischemia-reperfusion damage. The observation that RIPK3 ablation rescues embryonic lethality in mice deficient in caspase-8 or Fas-associated-protein-via-a-death-domain demonstrates the crucial role of this apoptotic platform in the negative control of necroptosis during development. Here, we review and discuss commonalities and differences of the increasing list of inducers of regulated necrosis ranging from cytokines, pathogen-associated molecular patterns, to several forms of physicochemical cellular stress. Since the discovery of the crucial role of RIPK1 and RIPK3 in necroptosis, these kinases have become potential therapeutic targets. The availability of new pharmacological inhibitors and transgenic models will allow us to further document the important role of this form of cell death in degenerative, inflammatory and infectious diseases.

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“…Necrosis was found to be the principal procedure of cell death in colon adenocarcinoma HT-29 cells [90]. This occurred irrespectively of different PDT doses and the absence of anti-apoptotic Bcl-2 expression.…”

Section: Photodynamic Therapy (Pdt) and Cancermentioning

confidence: 99%

Hypericins as Potential Leads for New Therapeutics

Karioti

Bilia

2010

IJMS

255

191

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70 years have passed since the first isolation of the naphthodianthrones hypericin and pseudohypericin from Hypericum perforatum L. Today, they continue to be one of the most promising group of polyphenols, as they fascinate with their physical, chemical and important biological properties which derive from their unique chemical structure. Hypericins and their derivatives have been extensively studied mainly for their antitumor, antiviral and antidepressant properties. Notably, hypericin is one of the most potent naturally occurring photodynamic agents. It is able to generate the superoxide anion and a high quantum yield of singlet oxygen that are considered to be primarily responsible for its biological effects. The prooxidant photodynamic properties of hypericin have been exploited for the photodynamic therapy of cancer (PDT), as hypericin, in combination with light, very effectively induces apoptosis and/or necrosis of cancer cells. The mechanism by which these activities are expressed continues to be a main topic of discussion, but according to scientific data, different modes of action (generation of ROS & singlet oxygen species, antiangiogenesis, immune responces) and multiple molecular pathways (intrinsic/extrinsic apoptotic pathway, ERK inhibition) possibly interrelating are implicated. The aim of this review is to analyse the most recent advances (from 2005 and thereof) in the chemistry and biological activities (in vitro and in vivo) of the pure naphthodianthrones, hypericin and pseudohypericin from H. perforatum. Extracts from H. perforatum were not considered, nor pharmakokinetic or clinical data. Computerised literature searches were performed using the Medline (PubMed), ChemSciFinder and Scirus Library databases. No language restrictions were imposed.

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Necrosis predominates in the cell death of human colon adenocarcinoma HT-29 cells treated under variable conditions of photodynamic therapy with hypericin

Cited by 46 publications

References 40 publications

Alterations in dysadherin expression and F-actin reorganization: a possible mechanism of hypericin-mediated photodynamic therapy in colon adenocarcinoma cells

Alterations in dysadherin expression and F-actin reorganization: a possible mechanism of hypericin-mediated photodynamic therapy in colon adenocarcinoma cells

Many stimuli pull the necrotic trigger, an overview

Hypericins as Potential Leads for New Therapeutics

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