Inhibition of Invasion by Polyphenols from Citrus Fruit and Berries in Human Malignant Glioma Cells In Vitro

HARCHARAN KAUR ROOPRAI; MARIA CHRISTIDOU; SAMANTHA ANGEL MURRAY; DEREK DAVIES; RICHARD SELWAY; RICHARD W. GULLAN; GEOFFREY J. PILKINGTON

doi:10.21873/anticanres.14813

Abstract

Background/Aim: The outlook for patients with high grade glioma (HGG) remains dismal. Hence, attention has focused on numerous innovative treatments. Our group has proposed a strategy on the use of a combination of polyphenols, as anti-invasive agents for the management of these neoplasms. Materials and Methods: The aim of this study was to evaluate the in vitro effects of citrus flavonoids (tangeretin, nobiletin, naringin and limonin) and berry extracts (chokeberry, elderberry and bilberry) on selected mediators of invasion in 2 HGG cell cultures. Results: The IC₅₀ values could only be determined for tangeretin and chokeberry extract. The rest were non-functional in this context. Immunocytochemistry and flow cytometry results showed that chokeberry extract was most effective in down-regulating the expression of CD44. Similarly, RT-PCR data supported its ability to reduce gene expression of MMP-14 and EGFR. 2D invasion assays confirmed that inhibition is greater with chokeberry extract. Conclusion: Both polyphenols have anti-invasive potential but chokeberry extract is a stronger agent for glioma management.

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Authors’ Contributions
HKR and GJP designed the study. RS and RWG provided surgical samples and reviewed the work. MC, SAM and DD contributed to experimental studies and data analysis. HKR wrote the manuscript. All Authors read and approved the final manuscript.
This article is freely accessible online.
Conflicts of Interest
The Authors declare that they have no competing interests in relation to this study.
Funding
Financial support for this study was provided by the late Dennis Roth (Have a Chance Inc., USA), Golden Charitable Trust and UK Brain Tumour Society, UK.