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

Abstract

Recently an enhancement of the sensitivity of colorectal cancer (CRC) cells by 5-fluorouracil (5FU) due to the concurrent treatment with epigallocatechin-3gallate (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.

Combination Chemotherapy with Selected Polyphenols in Preclinical and Clinical Studies—An Update Overview

“…Moreover, EGCG effectively decreased the dose of DOX needed to reach cytotoxicity by mediating P-gp activity in the Caco-2 cell line [182]. Similarly, EGCG and 5-FU synergistic effects have been reported in other colon and CRC cell lines as well [183,184]. La et al carried out an in vitro and in vivo investigation and described how EGCG managed to enhance the sensitivity of colon cancer cells to 5-FU by inhibiting the GRP78/NF-κB/miR-155-5p/MDR1 pathway and by promoting 5-FU accumulation in cancer cells [185].…”

“…Polonio-Alcalá et al demonstrated that EGCG combination with either GEF or osimertinib (OSM) resulted in mostly additive effects [179], while another study described how EGCG overcame GEF resistance in NSCLC through inhibiting autophagy and enhancing cell death by inhibiting the Raf/MEK/ERK pathway [180] (Table 4, Figure 4). [175][176][177][178][179][180], colorectal [181][182][183][184][185][186][187], liver [188], gastric [189] and breast [190][191][192][193] cancer) and clinical (lung [194][195][196] and breast [197,198] colorectal [181][182][183][184][185][186][187], liver [188], gastric [189] and breast [190][191][192][193] cancer) and clinical (lung [194][195][196] and breast [197,…”

“…Figure 4. Combination of epigallocatechin gallate and chemotherapy in preclinical (lung[175][176][177][178][179][180], colorectal[181][182][183][184][185][186][187], liver[188], gastric[189] and breast[190][191][192][193] cancer) and clinical (lung[194][195][196] and breast[197,198] cancer) studies in the past five years. ; CIS: cisplatin; DOX: doxorubicin; 5-FU: 5-fluorouracil; ETO: etoposide; GEF: gefitinib; OSM: osimertinib; IRI: irinotecan; SOR: sorafenib; ATO: arsenic trioxide; CLF: clofarabine; SAHA: suberoylanilide hydroxamic acid.…”

In Vitro Assessment of the Synergistic Effect of Aspirin and 5-Fluorouracil in Colorectal Adenocarcinoma Cells

“…Furthermore, when the compounds were associated, the cytotoxic effect was enhanced, with approximately 13% of the cells remaining viable. A thorough review of the literature in the field led to the selection of the concentrations of 5-FU used in this study [51][52][53]. A study conducted by Srimuangwong et al assessed the effects of 5-FU at doses between 5 and 25 µmol/L on HT-29 cells, and it was found that the concentration of 25 µmol/L resulted in a reduction in viability below 80% after 48 h [54].…”