Reduced Susceptibility of Electroporated Tumor Cell Lines to Killing by Cytotoxic Lymphocytes

Dressel, Ralf; Baraki, Husnia; Langer, Frank; Günther, Eberhard

doi:10.1006/bbrc.1998.9302

Cited by 4 publications

(3 citation statements)

References 23 publications

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“…Other researchers have also demonstrated that EP induces the expression of HSP70 to a certain extent, as a result of environmental stress (57). However, another study demonstrated HSP70 induction may depend on the cell line (58). The data of the present study indicate that chemotherapeutic protocols may modulate expression of HSP27 and HSP70 in tumor tissues.…”

Section: A Sw626 24 H 48 H 72 H -supporting

confidence: 48%

Effect of electrochemotherapy with betulinic acid or cisplatin on regulation of heat shock proteins in metastatic human carcinoma cells in�vitro

et al. 2019

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Betulinic acid (BTA) is naturally occurring triterpene that has received interest as a novel therapeutic substance with cytotoxicity towards a number of cancer cell lines. Despite the wide spectrum of biological and pharmacological effects, its effect may be limited its lipophobic properties. Therefore, strategies to improve the access of BTA to the cells are required to enhance the anticancer effects. Electroporation (EP) enables increased inflow of drugs into cancer cells, even at low doses, which may reduce the side effects caused by high doses of chemotherapy. The potential application of BTA in electrochemotherapy (ECT) in metastatic type of cancers was investigated in the present study. The efficacy of BTA with EP was estimated using a cell survival assay (MTT assay), microscopical morphology analysis and the immunocytochemical expression of heat shock proteins (HSPs). HSPs are molecules that protect the cell from harmful environmental, chemical and physical stresses, and ensure cell survival, recovery and proper functioning. HSP expression is induced various stress factors. Therefore, the expression of HSP27 and HSP70 was evaluated after cells were exposed to an external pulsed electric field and anticancer drugs. Facilitated drug delivery and the anticancer effect on metastatic tumor cells were evaluated in vitro. The effect of BTA was compared with cisplatin (CP), a standard cytostatic agent. Two different metastatic cancer cell lines were used, an ovary adenocarcinoma cell line (SW626) and melanoma cell line (Me45). BTA combined with EP exhibited similar efficacy to CP with EP after 24 and 48 h in SW626 and Me45 cancer cells. Me45 cells also had high HSP27 and low HSP70 immunosignals post-ECT treatment. ECT caused increased expression of HSP27 and HSP70 proteins in SW626 cells, which were less sensitive to ECT than the Me45 melanoma cell line. The results indicate that BTA may be efficiently applied instead of CP in ECT approaches, but its activity differs between tumor cell lines.

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Section: A Sw626 24 H 48 H 72 H -supporting

confidence: 48%

Effect of electrochemotherapy with betulinic acid or cisplatin on regulation of heat shock proteins in metastatic human carcinoma cells in�vitro

et al. 2019

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“…Furthermore, the unchanged level of HSP 70 protein provides evidence that electroporation with up to 40 V did not elicit protein damage and, possibly, no DNA damage either. Other investigators showed that the exposure of human leukemic K562 cells to higher electric fields (from 100 to 500 V/cm) produced a weak but longlasting expression of HSP 70-2 mRNA (38). This could imply that our electroporation conditions were not sufficient to stimulate detectable induction of stress proteins.…”

Section: Discussionmentioning

confidence: 83%

The endothelial cytoskeleton as a target of electroporation-based therapies

Kanthou

Kranjc

Serša

et al. 2006

Molecular Cancer Therapeutics

107

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Electroporation-based therapies, such as electrochemotherapy and electrogene therapy, result in the disruption of blood vessel networks in vivo and cause changes in blood flow and vascular permeability. The effects of electroporation on the cytoskeleton of cultured primary endothelial cells and on endothelial monolayer permeability were investigated to elucidate possible mechanisms involved. Human umbilical vein endothelial cells (HUVECs) were electroporated in situ and then immunofluorescence staining for filamentous actin, B-tubulin, vimentin, and VE-cadherin as well as Western blotting analysis of levels of phosphorylated myosin light chain and cytoskeletal proteins were performed. Endothelial permeability was determined by monitoring the passage of FITC-coupled dextran through endothelial monolayers. Exposure of endothelial cells to electric pulses resulted in a profound disruption of microfilament and microtubule cytoskeletal networks, loss of contractility, and loss of vascular endothelial cadherin from cell-to-cell junctions immediately after electroporation. These effects were voltage dependent and reversible because cytoskeletal structures recovered within 60 min of electroporation with up to 40 V, without any significant loss of cell viability. The cytoskeletal effects of electroporation were paralleled by a rapid increase in endothelial monolayer permeability. These results suggest that the remodeling of the endothelial cytoskeleton and changes in endothelial barrier function could contribute to the vascular disrupting actions of electroporation-based therapies and provide an insight into putative mechanisms responsible for the observed increase in permeability and cessation of blood flow in vivo.

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“…Differences between allospecific lysis of cells treated with doxycycline and those left untreated (including E/T ratios of 100/1, 50/1, 25/1 and 12.5/1) were evaluated using nonparametric methods for repeated measurement analysis [47,48].…”

Section: Statisticsmentioning

confidence: 99%

Enhanced susceptibility to cytotoxic T lymphocytes without increase of MHC class I antigen expression after conditional overexpression of heat shock protein 70 in target cells

et al. 1999

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Antigenic peptides have been found associated with heat shock proteins (HSP) including cytoplasmic HSP70 and heat shock cognate protein 70 as well as the endoplasmic reticulum‐resident glucose‐regulated protein 94. Recently, HSP70 transfection has been reported to increase MHC class I cell surface expression and antigen presentation on mouse melanoma B16 cells (Wells et al., Int. Immunol. 1998. 10: 609). To analyze the effect of HSP70 on MHC class I cell surface expression and lysability of target cells we transfected a human melanoma cell line with the rat Hsp70‐1 gene using the Tet‐On system for conditional overexpression of HSP70. Induction of HSP70 did not increase cell surface expression of HLA class I molecules in general or individual HLA‐A and B antigens in particular. Nonetheless, induction of HSP70 enhanced susceptibility of these cells to lysis by allospecific CTL. The same effect was observed using an HLA‐A2‐restricted tyrosinase‐specific CTL clone after pulsing the tyrosinase‐negative target cells with the specific peptide. Thus, HSP70 induction can increase killing by CTL without affecting MHC class I cell surface expression or antigen processing. This effect of HSP70 appears to be different from the commonly found protection exerted by HSP70 against stress like heat shock, and might be mediated by improving CTL‐induced apoptosis.

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Reduced Susceptibility of Electroporated Tumor Cell Lines to Killing by Cytotoxic Lymphocytes

Cited by 4 publications

References 23 publications

Effect of electrochemotherapy with betulinic acid or cisplatin on regulation of heat shock proteins in metastatic human carcinoma cells in�vitro

Effect of electrochemotherapy with betulinic acid or cisplatin on regulation of heat shock proteins in metastatic human carcinoma cells in�vitro

The endothelial cytoskeleton as a target of electroporation-based therapies

Enhanced susceptibility to cytotoxic T lymphocytes without increase of MHC class I antigen expression after conditional overexpression of heat shock protein 70 in target cells

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