Oncotarget

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An investigation on [5 fluorouracil and epigallocatechin-3-gallate] complex activity on HT-29 cell death and its stability in gastrointestinal fluid

Laura Moracci _, Francesca Sensi, Andrea Biccari, Sara Crotti, Elisa Gaio, Federico Benetti, Pietro Traldi, Salvatore Pucciarelli and Marco Agostini _

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Oncotarget. 2022; 13:476-489. https://doi.org/10.18632/oncotarget.28207

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Abstract

Laura Moracci1,2, Francesca Sensi1,3, Andrea Biccari1,2, Sara Crotti1,2, Elisa Gaio4, Federico Benetti4, Pietro Traldi1, Salvatore Pucciarelli1,2 and Marco Agostini1,2

1 Nano-Inspired Biomedicine Lab, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padova, Italy

2 General Surgical Clinic 3, Department of Surgical, Oncological and Gastroentrological Sciences, University of Padua, Padova, Italy

3 Department of Molecular Sciences and Nanosystems, Ca’ Foscari University of Venice, Mestre, Venice, Italy

4 ECSIN-European Center for the Sustainable Impact of Nanotechnology, ECAMRICERT SRL, Padova, Italy

Correspondence to:

Laura Moracci, email: laura-moracci@libero.it
Marco Agostini, email: m.agostini@unipd.it

Keywords: HT29; 5-fluorouracil; epigallocatechin-3-gallate; molecular complexes; gastrointestinal model

Received: December 17, 2021     Accepted: February 17, 2022     Published: March 03, 2022

Copyright: © 2022 Moracci et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Recently an enhancement of the sensitivity of colorectal cancer (CRC) cells by 5-fluorouracil (5FU) due to the concurrent treatment with epigallocatechin-3-gallate (EGCG) has been found. In the present paper, to investigate on this aspect, adenocarcinoma cells HT29 were treated with 5FU, EGCG and an equimolar mixture of 5FU and EGCG ([5FU+EGCG]) and cell viability was determined. While 5FU exhibits a clear activity, EGCG alone does not express any activity. However by treating the cells with [5FU+EGCG] a strong effect of EGCG is evidenced: the sensitivity of HT29 cells to 5FU was increased by 12-fold. A simulation of the behavior of [5FU+EGCG] in different compartments of the gastrointestinal digestion model was also performed. 5FU and EGCG solubilized into a mixture of digestive fluids analyzed by mass spectrometry did not lead to signals of 5FU, EGCG and the related complex, while by diluting the solution they become detectable. On the contrary, when 5FU and EGCG are submitted to the step-by-step digestion model procedure, the analysis did not show the presence of 5FU, EGCG and [5FU+EGCG]. This behaviour could be ascribed to the instability of these compounds due to the too severe digestion conditions and/or to the complexity of the matrix which could lead in ESI conditions to the suppression of the signals of the analytes of interest.


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