. Int J Cancer. 2016 Aug 20. doi: 10.1002/ijc.30398. [Epub ahead of print]

Mukherjee S1, Baidoo J2, Fried A3, Atwi D3, Dolai S2, Boockvar J4, Symons M4, Ruggieri R4, Raja K2, Banerjee P2,3.

 

Author information:

1Department of Biochemistry, City University of New York at The College of Staten Island, NY, 10314.

2Department of Chemistry, City University of New York at The College of Staten Island, NY, 10314.

3Department of The Center for Developmental Neuroscience, CUNY Doctoral Programs, City University of New York at The College of Staten Island, NY, 10314.

4Center for Oncology and Cell Biology and Department of Neurosurgery and Otolaryngology/Head and Neck Surgery, The Feinstein Institute, Northwell Health, Manhasset, NY, 11030.

 

Abstract

 

Glioblastoma (GBM) is one of the most pernicious forms of cancer and currently chances of survival from this malady are extremely low. We have used the non-invasive strategy of intranasal (IN) delivery of a glioblastoma-directed adduct of curcumin (CC), CC-CD68Ab, into the brain of mouse GBM GL261-implanted mice to study the effect of CC on tumor remission and on the phenotype of the tumor-associated microglial cells (TAMs). The treatment caused tumor remission in 50% of GL261-implanted GBM mice. A similar rescue rate was also achieved through intraperitoneal infusion of a lipid-encapsulated formulation of CC, Curcumin Phytosome, into the GL261-implanted GBM mice. Most strikingly, both forms of CC elicited a dramatic change in the tumor-associated Iba1+ TAMs, suppressing the tumor-promoting Arginase1high , iNOSlow M2-type TAM population while inducing the Arginase1low , iNOShigh M1-type tumoricidal microglia. Concomitantly, we observed a marked induction and activation of microglial NF-kB and STAT1, which are known to function in coordination to cause induction of iNOS. Therefore, our novel findings indicate that appropriately delivered CC can directly kill GBM cells and also repolarize the TAMs to the tumoricidal M1 state. This article is protected by copyright. All rights reserved.

 

© 2016 UICC.