Skip to main content
  • Intratumoral bioavailability and specific effects in Phosphoethanolamin-MRI of the solubilised natural compound curcumin in glioblastoma patients

    Final Number:

    Stephan Dützmann MD; Christina Schiborr; Alexa Kocher; Elke Hattingen MD; Jakob Weissenberger; Florian Geßler MD; Johanna Quick MD; Kea Franz MD; Volker Seifert MD, PhD; Jan Frank PhD; Christian Senft MD, PhD

    Study Design:
    Clinical Trial

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2013 Annual Meeting

    Introduction: Curcumin is intensely investigated in numerous cancer types as a potential natural antitumoral agent. We previously reported on the anti-proliferative, anti-migratory and anti-invasive properties of the natural, nontoxic compound curcumin on glioblastoma cell lines and mouse models. In this prospective clinical trial in glioblastoma patients we sought to determine the intratumoral concentrations and clinical tolerance of solubilised curcumin and detect subtle changes in pioneering Phosphorus MR spectroscopic imaging(31P MRSI)to measure biological phosphate compounds. To enhance the bioavailability of curcumin we used an innovative liquid solution (“solubilisate”) with a colloidal micelle-like structure creating an ultrafine distribution of curcumin that can be taken as a beverage.

    Methods: In this prospective trial, thirteen patients scheduled for surgery of suspected newly diagnosed glioblastoma drank four days before surgery 1g of solubilised curcumin in a 200mL beverage of pear-juice three times per day after regular meals. Furthermore,before and after the period of intake,a 31P MRSI was performed to detect subtle changes in the tumoral metabolism.The concentration of total curcumin was analysed in tissue and blood samples using High Performance Liquid Chromatography.

    Results: Three patients discontinued the study because of nausea. They were excluded as well as one patient who developed pneumonia after drinking one beverage. In the remaining nine patients the mean intratumoral concentration of curcumin was 56 pg/mg of tissue (range 9-151).The mean serum concentration was 253 ng/mL (range 129-364). Inorganic phosphate showed a trend to increase within the tumor(p<0.1)as detected by 31P MRSI.The tumor volume of one patient decreased by 10% after ingestion of curcumin.All patients had stool softness because of the beverage.One patient developed a reversible skin rash.

    Conclusions: Here we report the highest serum concentration of curcumin detected in clinical studies so far. The trend toward an increase of inorganic phosphate within the tumor(p<0.1)might be due to curcumin-induced damage to mitochondrial pathways.Further studies are needed to determine its specific effects and the molecular profiles of patients that might benefit from oral ingestion of this natural compound.

    Patient Care: Develop novel readily available therapies in the treatment of glioblastoma.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the importance of curcumin as a potential natural therapeutic in glioblastoma 2) Discuss, in small groups the relevance of changes in Phosphoethanolamin-MRI in glioblastoma patients

    References: 1. Lopez-Lazaro M. Anticancer and carcinogenic properties of curcumin: considerations for its clinical development as a cancer chemopreventive and chemotherapeutic agent. Molecular nutrition & food research. Jun 2008;52 Suppl 1:S103-127. 2. 3. Aggarwal BB, Shishodia S. Suppression of the nuclear factor-kappaB activation pathway by spice-derived phytochemicals: reasoning for seasoning. Annals of the New York Academy of Sciences. Dec 2004;1030:434-441. 4. Aggarwal BB, Shishodia S, Takada Y, et al. Curcumin suppresses the paclitaxel-induced nuclear factor-kappaB pathway in breast cancer cells and inhibits lung metastasis of human breast cancer in nude mice. Clin Cancer Res. Oct 15 2005;11(20):7490-7498. 5. Aggarwal S, Ichikawa H, Takada Y, Sandur SK, Shishodia S, Aggarwal BB. Curcumin (diferuloylmethane) down-regulates expression of cell proliferation and antiapoptotic and metastatic gene products through suppression of IkappaBalpha kinase and Akt activation. Molecular pharmacology. Jan 2006;69(1):195-206. 6. Anto RJ, Mukhopadhyay A, Denning K, Aggarwal BB. Curcumin (diferuloylmethane) induces apoptosis through activation of caspase-8, BID cleavage and cytochrome c release: its suppression by ectopic expression of Bcl-2 and Bcl-xl. Carcinogenesis. Jan 2002;23(1):143-150. 7. Senft C, Polacin M, Priester M, Seifert V, Kogel D, Weissenberger J. The nontoxic natural compound Curcumin exerts anti-proliferative, anti-migratory, and anti-invasive properties against malignant gliomas. BMC cancer.10:491. 8. Weissenberger J, Priester M, Bernreuther C, et al. Dietary curcumin attenuates glioma growth in a syngeneic mouse model by inhibition of the JAK1,2/STAT3 signaling pathway. Clin Cancer Res. Dec 1;16(23):5781-5795. 9. Dhillon N, Aggarwal BB, Newman RA, et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res. Jul 15 2008;14(14):4491-4499. 10. Gota VS, Maru GB, Soni TG, Gandhi TR, Kochar N, Agarwal MG. Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers. Journal of agricultural and food chemistry. Feb 24;58(4):2095-2099.

We use cookies to improve the performance of our site, to analyze the traffic to our site, and to personalize your experience of the site. You can control cookies through your browser settings. Please find more information on the cookies used on our site. Privacy Policy