Curcumin blocks brain tumor formation
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Sudarshana Purkayasthaa, b, Alexandra Berlinerb, Suraj Shawn Fernandoa, b, Buddima Ranasinghea, c, Indrani Raya, b, Hussnain Tariqa, b and Probal Banerjeea, b, c, Corresponding Author Contact Information, E-mail The Corresponding Author

aDepartment of Chemistry, The College of Staten Island (CUNY), Staten Island, NY 10314, USA

bThe CSI/IBR Center for Developmental Neuroscience, The College of Staten Island (CUNY), Staten Island, NY 10314, USA

cCUNY Doctoral Program in Biochemistry, The College of Staten Island (CUNY), Staten Island, NY 10314, USA
Accepted 24 January 2009.
Available online 11 February 2009.

Abstract

Turmeric, an essential ingredient of culinary preparations of Southeast Asia, contains a major polyphenolic compound, named curcumin or diferuloylmethane, which eliminates cancer cells derived from a variety of peripheral tissues. Although in vitro experiments have addressed its anti-tumor property, no in vivo studies have explored its anti-cancer activity in the brain. Oral delivery of this food component has been less effective because of its low solubility in water. We show that a soluble formulation of curcumin crosses the blood–brain barrier but does not suppress normal brain cell viability. Furthermore, tail vein injection, or more effectively, intracerebral injection through a cannula, blocks brain tumor formation in mice that had already received an intracerebral bolus of mouse melanoma cells (B16F10). While exploring the mechanism of its action in vitro we observed that the solubilized curcumin causes activation of proapoptotic enzymes caspase 3/7 in human oligodendroglioma (HOG) and lung carcinoma (A549) cells, and mouse tumor cells N18 (neuroblastoma), GL261 (glioma), and B16F10. A simultaneous decrease in cell viability is also revealed by MTT assays. Further examination of the B16F10 cells showed that curcumin effectively suppresses Cyclin D1, P-NF-kB, BclXL, P-Akt, and VEGF, which explains its efficacy in blocking proliferation, survival, and invasion of the B16F10 cells in the brain. Taken together, solubilized curcumin effectively blocks brain tumor formation and also eliminates brain tumor cells. Therefore, judicious application of such injectable formulations of curcumin could be developed into a safe therapeutic strategy for treating brain tumors.

Keywords: Curcumin; Brain tumor; Oligodendroglioma; Neuroblastoma; Cancer; Infiltrating melanoma; Apoptosis; Necrosis

Abbreviations: MTT, ; HPLC, high performance liquid chromatography; PI-3K, phosphoinositol-3-kinase; Erk, extracellular signal-regulated kinase; DMSO, dimethyl sulfoxide; PMSF, phenylmethylsulfonyl fluoride; PBS, phosphate buffered saline (10 mM); FBS, fetal bovine serum; Pen-Strep, penicillin–streptomycin
Article Outline

1. Introduction
2. Results

2.1. Solubilized curcumin crosses the blood–brain barrier, but it does not cause injury to normal brain cells
2.2. Solubilized curcumin blocks brain tumor formation
2.3. Solubilized curcumin causes a dramatic increase in caspase-3/7 activity in a wide variety of cancer cells
2.4. Solubilized curcumin results in a marked decrease in the viability of cancer cells
2.5. Solubilized curcumin causes suppression of tumor-promoting signaling proteins

3. Discussion
4. Experimental procedures

4.1. Materials
4.2. Culturing cell lines
4.3. Solubilization of curcumin and testing its ability to cross the blood–brain barrier
4.4. MTT assay to monitor the effect of solubilized curcumin on normal brain cells
4.5. Generating tumors in C57BL6 mice and blockage of tumor formation with solubilized curcumin
4.6. Delivery of B16F10 cells and solubilized curcumin using a cannula
4.7. Hematoxylin and eosin (H&E) staining of tissue sections
4.8. Treatment of cancer cells with solubilized curcumin
4.9. Western blot analysis
4.10. Caspase-3/7 assay
4.11. Cell viability assay using MTT

5. Conflict of interest
Acknowledgements
Appendix A. Supplementary data
References