Experimental and clinical studies on radiation and curcumin in human glioma

Peter Sminia,Jaap Van Den Berg,Wilko F A R Verbakel,Ben J Slotman,Eline Hageman,Arthur Van Kootwijk

doi:10.1007/s00432-020-03432-2

Abstract

PurposeThere is progressing evidence for the anti-cancer potential of the natural compound and dietary spice curcumin. Curcumin has been ascribed to be cytotoxic for various tumour cell types, to inhibit cell proliferation and to interfere with the cellular oxidant status. The compound has been notified as a therapeutic agent with radiosensitizing potential in brain tumour therapy. We considered the rationale to combine curcumin with radiation in the treatment of human glioblastoma multiforme (GBM).MethodDetermination of clonogenic cell survival following exposure of U251 human glioma cells to single dose (1–6 Gy) and fractionated irradiation (5 daily fractions of 2 Gy) without and with curcumin. Additional literature search focused on the interaction between curcumin and radiotherapy in experimental and clinical studies on human glioma.ResultsNo interaction was found on the survival of U251 human glioma cells after irradiation in combination with curcumin at clinically achievable concentrations. Experimental in vitro and in vivo data together with clinical bioavailability data from the literature do not give evidence for a radiosensitizing effect of curcumin. Reported GBM intratumoural curcumin concentrations are too low to either exert an own cytotoxic effect or to synergistically interact with radiation. Novel approaches are being explored to increase the bioavailability of curcumin and to facilitate transport over the blood–brain barrier, aimed to reach therapeutic curcumin levels at the tumour site.ConclusionThere is neither a biological nor clinical rationale for using curcumin as radiosensitizer in the therapy of GBM patients.

Highlights

Glioblastoma multiforme (GBM) is the most malignant and common human brain tumour
Three pilot experiments investigating the effect on cell proliferation and clonogenic cell survival of (1) long-term (96 h) exposure and (2) shortexposure duration (2 h) to a range of curcumin doses and (3) 0–3 h to 100 μM curcumin
In the dose range of 10–20 μM, suppressed E3 ubiquitin–protein ligase NEDD4 (Neural precursor cell Expressed Developmentally Downregulated protein 4) which is overexpressed in gliomas, leading to inhibition of cell proliferation, apoptosis, cell migration, and invasion (Wang et al 2017)

Summary

Introduction

GBM patients are generally treated according to the current standard protocol of surgery followed by radiotherapy and concomitant and adjuvant chemotherapy, typically with the alkylating agent temozolomide. Despite this aggressive multimodality therapy, patients’ survival at 5 years after diagnosis is still only a few percent (Stupp et al 2009). A large number of studies have revealed that curcumin, the principle ingredient of the Indian dietary spice turmeric (Curcuma longa), demonstrates anti-cancer properties in a variety of tumour types, including GBM (Hatcher et al 2008). Following repeated intake of curcumin in humans, blood serum concentration peaked at approximately 2 μM (Cheng et al 2001), which might be too low for anticancer efficacy. Mean intratumoural curcumin concentrations of approximately 0.15 μM have been reported after

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Conclusion