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

Toxins
Wendy S SmithD J Flavell

Abstract

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 th...Continue Reading

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Citations

Dec 25, 2019·Pharmaceutical Research·Harrison J WensleyDavid J Flavell
Jan 18, 2020·Expert Opinion on Drug Delivery·Reza Baradaran EftekhariFarid Abedin Dorkoosh
Jan 19, 2021·Expert Opinion on Drug Delivery·Mohammad HajimolaaliFarid Dorkoosh
Nov 25, 2020·International Journal of Molecular Sciences·Wendy S SmithDavid J Flavell

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Methods Mentioned

BETA
flow cytometry
confocal microscopy
FCS
Flow
Assay

Software Mentioned

CytExpert
CellRox
EXPO32 ADC
Leica LAS - X
Graph Pad Prism

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