scholarly journals Augmentation of Saporin-Based Immunotoxins for Human Leukaemia and Lymphoma Cells by Triterpenoid Saponins: The Modifying Effects of Small Molecule Pharmacological Agents

Toxins ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 127 ◽  
Author(s):  
Wendy Smith ◽  
David Johnston ◽  
Suzanne Holmes ◽  
Harrison Wensley ◽  
Sopsamorn Flavell ◽  
...  
Keyword(s):  
Small Molecule ◽  
Target Antigen ◽  
Cytotoxic Action ◽  
Lymphoma Cells ◽  
Pharmacological Agents ◽  
Triterpenoid Saponins ◽  
Endosomal Acidification ◽  
Human Lymphoma ◽  
Ros Scavenger ◽  
Human Leukaemia

Triterpenoid saponins from Saponinum album (SA) significantly augment the cytotoxicity of saporin-based immunotoxins but the mechanism of augmentation is not fully understood. We investigated the effects of six small molecule pharmacological agents, which interfere with endocytic and other processes, on SA-mediated augmentation of saporin and saporin-based immunotoxins (ITs) directed against CD7, CD19, CD22 and CD38 on human lymphoma and leukaemia cell lines. Inhibition of clathrin-mediated endocytosis or endosomal acidification abolished the SA augmentation of saporin and of all four immunotoxins tested but the cytotoxicity of each IT or saporin alone was largely unaffected. The data support the hypothesis that endocytic processes are involved in the augmentative action of SA for saporin ITs targeted against a range of antigens expressed by leukaemia and lymphoma cells. In addition, the reactive oxygen species (ROS) scavenger tiron reduced the cytotoxicity of BU12-SAP and OKT10-SAP but had no effect on 4KB128-SAP or saporin cytotoxicity. Tiron also had no effect on SA-mediated augmentation of the saporin-based ITs or unconjugated saporin. These results suggest that ROS are not involved in the augmentation of saporin ITs and that ROS induction is target antigen-dependent and not directly due to the cytotoxic action of the toxin moiety.

scholarly journals The Effect of Small Molecule Pharmacological Agents on the Triterpenoid Saponin Induced Endolysosomal Escape of Saporin and a Saporin-Based Immunotoxin in Target Human Lymphoma Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 300
Author(s):  
Harrison J. Wensley ◽  
Wendy S. Smith ◽  
Suzanne E. Holmes ◽  
Sopsamorn U. Flavell ◽  
David J. Flavell
Keyword(s):  
Pulse Shape ◽  
Leukemia Cell ◽  
Triterpenoid Saponin ◽  
Direct Role ◽  
Pharmacological Agents ◽  
Triterpenoid Saponins ◽  
Flow Cytometric ◽  
Leukemia Cell Lines ◽  
Endosomal Acidification ◽  
Human Lymphoma

Triterpenoid saponins augment the cytotoxicity of saporin based immunotoxins. It is postulated that this results from a saponin-mediated increase in the endolysosomal escape of the toxin to the cytosol, but this remains to be confirmed. To address this issue, we used a number of pharmacological inhibitors of endocytic processes as probes to investigate the role played by saponin in the endolysosomal escape of fluorescently labeled saporin and a saporin based immunotoxin targeted against CD38 on human lymphoma and leukemia cell lines. Endolysosomal escape of the toxin was measured by flow cytometric pulse shape analysis. These results were compared to the effects of the various inhibitors on the saponin-mediated augmentation of toxin and immunotoxin cytotoxicity. Inhibitors of clathrin-mediated endocytosis, micropinocytosis, and endosomal acidification abrogated the saponin-induced increase in the endolysosomal escape of the toxin into the cytosol, suggesting that these processes may be involved in the internalization of saponin to the same endolysosomal vesicle as the toxin. Alternatively, these processes may play a direct role in the mechanism by which saponin promotes toxin escape from the endolysosomal compartment to the cytosol. Correlation with the effects of these inhibitors on the augmentation of cytotoxicity provides additional evidence that endolysosomal escape is involved in driving augmentation.

Involvement of both caspase-dependent and -independent pathways in apoptotic induction by hexaminolevulinate-mediated photodynamic therapy in human lymphoma cells

APOPTOSIS ◽  
2006 ◽  
Vol 11 (11) ◽  
pp. 2031-2042 ◽  
Author(s):  
Ingegerd Eggen Furre ◽  
Michael T. N. Møller ◽  
Susan Shahzidi ◽  
Jahn M. Nesland ◽  
Qian Peng
Keyword(s):  
Photodynamic Therapy ◽  
Lymphoma Cells ◽  
Human Lymphoma ◽  
Apoptotic Induction

Activation of JNK and c-Jun is involved in glucose oxidase-mediated cell death of human lymphoma cells

2009 ◽  
Vol 28 (6) ◽  
pp. 545-551 ◽  
Author(s):  
Young-Ok Son ◽  
Yong-Suk Jang ◽  
Xianglin Shi ◽  
Jeong-Chae Lee
Keyword(s):  
Cell Death ◽  
Glucose Oxidase ◽  
Lymphoma Cells ◽  
Human Lymphoma

scholarly journals Adhesion to high endothelial venules: a model for dissemination mechanisms in non-Hodgkin's lymphoma

Blood ◽  
1993 ◽  
Vol 82 (1) ◽  
pp. 262-267 ◽  
Author(s):  
R Stauder ◽  
S Hamader ◽  
B Fasching ◽  
G Kemmler ◽  
J Thaler ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Lymphocytic Leukemia ◽  
Hodgkin's Lymphoma ◽  
Lymphoma Cells ◽  
High Endothelial Venules ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Human Lymphoma ◽  
Binet Stage

The interaction of human lymphoma cells with high endothelial venules (HEVs) on sections of lymphatic tissues was studied in 44 cases of non- Hodgkin's lymphoma (NHL) with the in vitro HEV binding assay. The relative adherence ratio (RAR) of lymphoma cells to HEVs as related to that of reactive lymphocytes was 0.29 to 4.64 in 38 cases of B chronic lymphocytic leukemia (CLL), 1.15 and 1.54 in two cases of immunocytic NHL, 1.12 and 0.70 in two cases of centrocytic NHL, 1.98 in one case of a peripheral T-NHL, whereas plasma cell leukemia cells adhered very weakly (RAR 0.1). Among the patients suffering from CLL a pronounced HEV binding ability of tumor cells correlated significantly with the more unfavorable Binet stages B and C (median 1.32) as well as with a widespread lymphatic dissemination, which strongly indicates a hematogenous, HEV-mediated spread (median 1.34). In contrast, weak adherence to HEVs was associated with Binet stage A (median 0.85; P < .05) and with a lacking or only localized clinical involvement of lymph nodes (median 0.84; P < .01). Thus, specific HEV recognition processes even operate in lymphoid neoplasms and via this mechanism seem to influence the dissemination of tumors.

scholarly journals Label-free impedance flow cytometry for nanotoxicity screening

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Melanie Ostermann ◽  
Alexander Sauter ◽  
Ying Xue ◽  
Eivind Birkeland ◽  
Julia Schoelermann ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Human Health ◽  
Trypan Blue ◽  
Label Free ◽  
Trigger Level ◽  
Lymphoma Cells ◽  
Human Lymphoma ◽  
Buffer Composition ◽  
Cost Efficient

AbstractThe development of reliable and cost-efficient methods to assess the toxicity of nanomaterials (NMs) is critical for the proper identification of their impact on human health and for ensuring a safe progress of nanotechnology. In this study, we investigated the reliability and applicability of label-free impedance flow cytometry (IFC) for in vitro nanotoxicity screening, which avoids time-consuming labelling steps and minimizes possible NM-induced interferences. U937 human lymphoma cells were exposed for 24 h to eight different nanomaterials at five concentrations (2, 10, 20, 50, and 100 μg/mL). The NMs’ effect on viability was measured using IFC and the results were compared to those obtained by trypan blue (TB) dye exclusion and conventional flow cytometry (FC). To discriminate viable from necrotic cells, the IFC measurement settings regarding signal trigger level and frequency, as well as the buffer composition, were optimised. A clear discrimination between viable and necrotic cells was obtained at 6 MHz in a sucrose-based measurement buffer. Nanomaterial-induced interferences were not detected for IFC. The IFC and TB assay results were in accordance for all NMs. The IFC was found to be robust, reliable and less prone to interferences due to the advantage of being label-free.

Sign in / Sign up

Export Citation Format

Share Document