Quercetin potentiates the effect of γδ T cells via modulating the expressions of Granzyme B, perforin and IFN-γ and also regulates the Wnt/β-catenin signalling pathway in human colon cancer cells

Hai-Yan Lu,Xiang-Dang Hu,Min Luo,Yong-Heng He,Tian-Shu Peng,Tian Nie,Shuai-Jun Li

doi:10.3329/bjp.v10i2.20387

Abstract

<p>Cancer accounts as one of the leading causes of morbidity and mortality. Recent studies focus on the efficiency of phytochemicals in cancer therapy. Influence of quercetin, a flavonoid on the effect of γδ T cells and Wnt/β-catenin signalling pathway in human colon cancer cells (HT55 and HCT116) was investigated. Quercetin at 15-120 µM was observed to markedly reduce the viability of HT55 and HCT116 cells. Quercetin exposure significantly increased γδ T cell proliferation and also raised the expressions of granzyme B (Gra B), perforin (PFP), and interferon- γ (IFN-γ) in γδ T cells. Reduced β-catenin expression with increased expressions of phosphorylated- β-catenin, axin1 and 2 were observed in HT55 and HCT116 cells on exposure to quercetin. However β-actin expression was found to be not much altered. The results suggest that quercetin was able to efficiently potentiate the effect of γδ T cells and modulate Wnt/β-catenin signalling pathway.</p><p> </p>

Highlights

Colon cancer has multiple transition steps due to the accrual of genetic errors in genes involved in apoptosis and cell proliferation (Davies et al, 2005; Watson, 2006)
Antibodies and reagents: Human Colon Cancer cell lines HT55 and HCT116 were obtained from Sigma-Aldrich, St
Monoclonal antibody fluorescein isothiocyanate (FITC)-conjugated anti- TCR, phycoerythrin (PE)-conjugated-anti-Granzyme B (GraB), PEconjugated anti-perforin (PFP), APC conjugated antiIFN- and control IgGs, mouse anti- catenin, mouse anti- -actin were purchased from BD Biosciences

Summary

Introduction

Colon cancer has multiple transition steps due to the accrual of genetic errors in genes involved in apoptosis and cell proliferation (Davies et al, 2005; Watson, 2006). The most frequent cause is the dysregulation of Wnt/ catenin signalling pathway that plays a vital role in normal cellular responses and in tumorigenesis (Logan and Nusse, 2004; Clevers, 2006). Genetic defects that lead to aberrant activation of Wnt/ -catenin signalling are reported in over 90% of sporadic colon cancer cases (Miyaki et al, 1994; Klaus and Birchmeier, 2008). Upon activation of Wnt signal, -catenin translocates into the nuclear region and forms a ternary complex with transcription factors - T-cell factor/ lymphoid enhancer factor to activate genes involved in cell proliferation (Reya and Clevers, 2005; Espada et al, 2009). Previous observations have recently aided the development of novel immunotherapeutic approaches aimed at T cell activation (Zhu et al, 2013)

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