The Activation of the c-Jun N-terminal Kinase and p38 Mitogen-activated Protein Kinase Signaling Pathways Protects HeLa Cells from Apoptosis Following Photodynamic Therapy with Hypericin

Assefa, Zerihun; Vantieghem, Annelies; Declercq, Wim; Vandenabeele, Peter; Vandenheede, Jackie R.; Merlevede, Wilfried; Witte, Peter de; Agostinis, Patrizia

doi:10.1074/jbc.274.13.8788

Cited by 205 publications

(160 citation statements)

References 53 publications

(70 reference statements)

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“…The caspase family has 14 members in mammals, including caspases -2, -8, -9, and -10 as initiators and caspases -3, -6, and -7 as executioners (Hostanska et al, 2003). Poly (ADP-ribose) polymerase (PARP) fragmentation, which is an indication of activation of the effector caspase-3, was the most important step during HYP-mediated cell death in cervical HeLa cells (Assefa et al, 1999). PARP cleavage was also observed in our study, in both HT-29 and Caco-2 cells, after HYP photoactivation (data not shown).…”

Section: Resultsmentioning

confidence: 99%

Evaluation of apoptotic cell death mechanisms induced by hypericin-mediated photodynamic therapy in colon cancer cells

Süloğlu¹,

Karacaoğlu²,

Selmanoğlu³

et al. 2016

Turk J Biol

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Hypericin (HYP)-mediated photodynamic therapy (PDT) is a new alternative treatment strategy for colon cancer inducing various cell-death pathways. Apoptotic cell death is the desired cellular fate in cancer cells. Therefore, we investigated the apoptotic pathways by determining apoptosis-related proteins (survivin, caspase-3, caspase-9, Bcl-2, and Bax) at the mRNA level using real-time polymerase chain reaction (qPCR), and the percentage of survivin was determined by survivin ELISA in HT-29 and Caco-2 colon cancer cell lines. The downregulation of survivin was significant 16 h after PDT for both cells, while caspase-3 upregulation was apparent 24 h after PDT. Caspase-9 and caspase-3 upregulations were parallel to each other. There was no Bcl-2 expression in HT-29 cells, but we observed downregulation in Bcl-2 expression in Caco-2 cells after HYP photoactivation. The Bax expression downregulated significantly after 24 h incubation in HT-29 cells, while it was upregulated after 16 h incubation in Caco-2 cells. The present study provides evidence that HYP-induced alterations in apoptosis-related protein expression ended in different responses in HT-29 and Caco-2 colon cancer cells, and these may be used in the treatment of chemotherapy-resistant cancer types.

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Section: Resultsmentioning

confidence: 99%

Evaluation of apoptotic cell death mechanisms induced by hypericin-mediated photodynamic therapy in colon cancer cells

Süloğlu¹,

Karacaoğlu²,

Selmanoğlu³

et al. 2016

Turk J Biol

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“…However, hypericin-PDT also activates rescuing responses, chiefly governed by the activation of p38 MAPK (Assefa et al, 1999;Hendrickx et al, 2003). p38 MAPK , of which four isoforms (p38-a, -b, -g and -d) exist, is a member of the mitogen-activated protein kinase (MAPK) superfamily commonly activated by cellular stress, proinflammatory cytokines and growth factors (Zarubin and Han, 2005).…”

Section: Introductionmentioning

confidence: 99%

Molecular effectors and modulators of hypericin-mediated cell death in bladder cancer cells

et al. 2007

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Photodynamic therapy (PDT) is an anticancer approach utilizing a light-absorbing molecule and visible light irradiation to generate, in the presence of O 2 , cytotoxic reactive oxygen species, which cause tumor ablation. Given that the photosensitizer hypericin is under consideration for PDT treatment of bladder cancer we used oligonucleotide microarrays in the T24 bladder cancer cell line to identify differentially expressed genes with therapeutic potential. This study reveals that the expression of several genes involved in various metabolic processes, stress-induced cell death, autophagy, proliferation, inflammation and carcinogenesis is strongly affected by PDT and pinpoints the coordinated induction of a cluster of genes involved in the unfolded protein response pathway after endoplasmic reticulum stress and in antioxidant response. Analysis of PDT-treated cells after p38 MAPK inhibition or silencing unraveled that the induction of an important subset of differentially expressed genes regulating growth and invasion, as well as adaptive mechanisms against oxidative stress, is governed by this stress-activated kinase. Moreover, p38 MAPK inhibition blocked autonomous regrowth and migration of cancer cells escaping PDT-induced cell death. This analysis identifies new molecular effectors of the cancer cell response to PDT opening attractive avenues to improve the therapeutic efficacy of hypericin-based PDT of bladder cancer.

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“…Also, expression of CrmA did not affect the kinetics of cytochrome C release Jurkat human lymphoma T cells [295] and procaspase-3 cleavage in a rat/mouse T cell hybridoma sensitized with hypericin [68], suggesting that caspase-8 does not play a major role in the demise process in this model. The activation of caspases in photosensitized cells leads to the cleavage of a number of other cell proteins, including Bap-31 (shuttle protein between the ER and the intermediate compartment and/or Golgi complex [71]), DNA-dependent protein kinase (catalytic subunit) (DNA-PK CS [75]), ICAD (inhibitor of caspase activated DNAse); prevents DNA fragmentation via binding to caspase-activated deoxyribonuclease [76]), focal adhesion kinase (FAK, a kinase involved in the regulation of cell adhesion [73]), lamins (structural components of the nuclear envelope [73]), PARP (poly(ADP-ribose) polymerase, a DNA repair enzyme [18,20,44,54,68,71,72,75,[77][78][79][80][81][82][83][84][85]) and Ras GTPase-activating protein (Ras-GAP, a negative regulator of the Ras signaling pathway [71]). DNA fragmentation in segments that are multiples of 180 -200 bp, another hallmark of apoptotic cell death [86], was also observed in PDT, using different cell types and sensitizers (Table 1).…”

Section: Role Of Caspases In Pdtmentioning

confidence: 99%

Intracellular signaling mechanisms in photodynamic therapy

Almeida

Manadas

Carvalho

et al. 2004

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

242

292

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In photodynamic therapy (PDT) a sensitizer, light and oxygen are used to induce death of tumor cells and in the treatment of certain noncancerous conditions. Cell death in PDT may occur by apoptosis or by necrosis, depending on the sensitizer, on the PDT dose and on the cell genotype. Some sensitizers that have been used in PDT are accumulated in the mitochondria, and this may explain their efficiency in inducing apoptotic cell death, both in vitro and in vivo. In this review we will focus on the events that characterize apoptotic death in PDT and on the intracellular signaling events that are set in motion in photosensitized cells. Activation of phospholipases, changes in ceramide metabolism, a rise in the cytosolic free Ca 2 + concentration, stimulation of nitric oxide synthase (NOS), changes in protein phosphorylation and alterations in the activity of transcription factors and on gene expression have all been observed in PDT-treated cells. Although many of these metabolic reactions contribute to the demise process, some of them may antagonize cell death. Understanding the signaling mechanisms in PDT may provide means to modulate the PDT effects at the molecular level and potentiate its antitumor effectiveness. D

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The Activation of the c-Jun N-terminal Kinase and p38 Mitogen-activated Protein Kinase Signaling Pathways Protects HeLa Cells from Apoptosis Following Photodynamic Therapy with Hypericin

Abstract: In this study, we elucidate signaling pathways induced by photodynamic therapy (PDT) with hypericin. We show that PDT rapidly activates JNK1 while irreversibly inhibiting ERK2 in several cancer cell lines. In HeLa cells, sustained PDT-induced JNK1 and p38 mitogen-activated protein kinase (

Cited by 205 publications

References 53 publications

Evaluation of apoptotic cell death mechanisms induced by hypericin-mediated photodynamic therapy in colon cancer cells

Evaluation of apoptotic cell death mechanisms induced by hypericin-mediated photodynamic therapy in colon cancer cells

Molecular effectors and modulators of hypericin-mediated cell death in bladder cancer cells

Intracellular signaling mechanisms in photodynamic therapy

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