Experimental and clinical studies on radiation and curcumin in human glioma
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ORIGINAL ARTICLE – CANCER RESEARCH
Experimental and clinical studies on radiation and curcumin in human glioma Peter Sminia1 · Jaap van den Berg1 · Arthur van Kootwijk1 · Eline Hageman1 · Ben J. Slotman1 · Wilko F. A. R. Verbakel1 Received: 15 May 2020 / Accepted: 19 October 2020 © The Author(s) 2020
Abstract Purpose There 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). Method Determination 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. Results No 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. Conclusion There is neither a biological nor clinical rationale for using curcumin as radiosensitizer in the therapy of GBM patients. Keywords Curcuma longa · Curcumin · Radiation · GBM · Nanoparticles · Radiosensitization
Introduction Glioblastoma multiforme (GBM) is the most malignant and common human brain tumour. 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). The poor treatment response of
* Peter Sminia [email protected] 1
Department of Radiation Oncology, Amsterdam University Medical Centers, VU University, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
GBMs has been ascribed to radioresistant glioma stem cells and phenotypic heterogeneity. 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 GB
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