An in vitro evaluation of epigallocatechin gallate (eGCG) as a biocompatible inhibitor of ricin toxin

Dyer, Paul D. R. and Kotha, Arun K. and Gollings, Alex S. and Shorter, Susan A. and Shepherd, Thomas R. and Pettit, Marie W. and Alexander, Bruce D. and Getti, Giulia T. M. and El-Daher, Samer and Baillie, Les and Richardson, Simon C. W. (2016) An in vitro evaluation of epigallocatechin gallate (eGCG) as a biocompatible inhibitor of ricin toxin. BBA - General Subjects, 1860 (7). pp. 1541-1550. ISSN 0304-4165

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Official URL: http://dx.doi.org/10.1016/j.bbagen.2016.03.024

Abstract

The catechin, epigallocatechin gallate (eGCG), found in green tea, has inhibitory activity against a number of protein toxins and was investigated in relation to its impact upon ricin toxin (RT) in vitro. The IC50 for RT was 0.08 ± 0.004 ng/mL whereas the IC50 for RT + 100 μM eGCG was 3.02 ± 0.572 ng/mL, indicating that eGCG mediated a significant (p < 0.0001) reduction in ricin toxicity. This experiment was repeated in the human macrophage cell line THP-1 and IC50 values were obtained for RT (0.54 ± 0.024 ng/mL) and RT + 100 μM eGCG (0.68 ± 0.235 ng/mL) again using 100 μM eGCG and was significant (p = 0.0013). The documented reduction in ricin toxicity mediated by eGCG was found to be eGCG concentration dependent, with 80 and 100 μg/mL (i.e. 178 and 223 μM respectively) of eGCG mediating a significant (p = 0.0472 and 0.0232) reduction in ricin toxicity at 20 and 4 ng/ml of RT in Vero and THP-1 cells (respectively). When viability was measured in THP-1 cells by propidium iodide exclusion (as opposed to the MTT assays used previously) 10 ng/mL and 5 ng/mL of RT was used. The addition of 1000 μM and 100 μM eGCG mediated a significant (p = 0.0015 and < 0.0001 respectively) reduction in ricin toxicity relative to an identical concentration of ricin with 1 μg eGCG. Further, eGCG (100 μM) was found to reduce the binding of RT B chain to lactose-conjugated Sepharose as well as significantly (p = 0.0039) reduce the uptake of RT B chain in Vero cells. This data suggests that eGCG may provide a starting point to refine biocompatible substances that can reduce the lethality of ricin.

Item Type: Journal Article
Keywords: Biophysics, Ricin toxin, Endocytosis, Polyphenol, Epigallocatechin gallate, eGCG, Tea, A-chain, Thearubigin fraction, Tea extract, Cells, Galactose, Delivery
Faculty: ARCHIVED Faculty of Science & Technology (until September 2018)
SWORD Depositor: Symplectic User
Depositing User: Symplectic User
Date Deposited: 15 Jan 2020 09:39
Last Modified: 15 Jan 2020 09:53
URI: http://arro.anglia.ac.uk/id/eprint/705092

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