Article
Intratumoral bioavailability and changes in Phosphoethanolamin-MRI of the solubilised natural compound curcumin in glioblastoma patients
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Authors
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Stephan Dützmann
- Klinik für Neurochirurgie, Universitätsklinikum der Johann Wolfgang Goethe Universität Frankfurt, Germany
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Christina Schiborr
- Institut für Biologische Chemie und Ernährung, Hohenheim Universität, Germany
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Alexa Kocher
- Institut für Biologische Chemie und Ernährung, Hohenheim Universität, Germany
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Elke Hattingen
- Institut für Neuroradiologie, Universitätsklinikum der Johann Wolfgang Goethe Universität Frankfurt, Germany
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Ulrich Pilatus
- Institut für Neuroradiologie, Universitätsklinikum der Johann Wolfgang Goethe Universität Frankfurt, Germany
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Jakob Weissenberger
- Klinik für Neurochirurgie, Universitätsklinikum der Johann Wolfgang Goethe Universität Frankfurt, Germany
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Florian Geßler
- Klinik für Neurochirurgie, Universitätsklinikum der Johann Wolfgang Goethe Universität Frankfurt, Germany
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Johanna Quick
- Klinik für Neurochirurgie, Universitätsklinikum der Johann Wolfgang Goethe Universität Frankfurt, Germany
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Kea Franz
- Klinik für Neurochirurgie, Universitätsklinikum der Johann Wolfgang Goethe Universität Frankfurt, Germany
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Volker Seifert
- Klinik für Neurochirurgie, Universitätsklinikum der Johann Wolfgang Goethe Universität Frankfurt, Germany
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Jan Frank
- Institut für Biologische Chemie und Ernährung, Hohenheim Universität, Germany
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Christian Senft
- Klinik für Neurochirurgie, Universitätsklinikum der Johann Wolfgang Goethe Universität Frankfurt, Germany
| Published: | June 2, 2015 |
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Outline
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Objective: Curcumin is intensely investigated in numerous other cancer types as a potential natural antitumoral agent. Here we sought to determine the intratumoral bioavailability and safety profile of solubilised curcumin in a prospective clinical trial in glioblastoma patients and detect curcumin 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") that has a colloidal micelle-like structure creating an ultrafine distribution of the curcumin and that can be taken as a beverage.
Method: 4 days before surgery patients that were scheduled for surgery for suspected newly diagnosed gliobastoma drank 1 g of solubilisated curcumin in a 0,2 L beverage of pear-juice 3 times per day after regular meals (in total 12 g). Furthermore, before and after the period of intake, a 31P MRSI was performed to detect subtle changes in the tumoral metabolism. Fresh frozen tissue was used to detect curcumin and its metabolites via mass spectroscopy.
Results: 13 patients could be included into the study up to date. 3 patients terminated the study early and were excluded because they developed nausea to the compound. 1 patient was excluded because he developed pneumonia after drinking 1 beverage.
Mean tumor concentration of curcumin was 56 pg/mg of tissue (range 9-151). Mean serum concentration was 253 ng/mL (range 129-364). Intratumoral pH was higher during curcumin administration at a significance level of 0,07. Anorganic phosphate showed a trend to increase within the tumor (p<0.1) as detected by 31P MRSI. The tumor of one patient shrank after ingestion of Curcumin by about 10%. All patients had stool softness because of the beverage. One patient developed a reversible skin rash.
Conclusions: Solubilised Curcumin is accumulated in glioblastomas. Further molecular studies are needed to determine its specific effects and molecular profiles of patients that might benefit from oral ingestion of this natural compound.
