title: Curcumin changes the polarity of tumor-associated microglia and eliminates glioblastoma.
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 noninvasive 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, iNOSlowM2-type TAM population while inducing the Arginase1low, iNOShighM1-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.
authors.affiliation: CUNY Doctoral Program In Biochemistry, CUNY Graduate Center, NY-10016.|Department of Chemistry, City University of New York at The College of Staten Island, NY, 10314.|The Center for Developmental Neuroscience, City University of New York at The College of Staten Island, NY, 10314.
authors.forename: Sumit
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: CUNY Doctoral Program In Biochemistry, CUNY Graduate Center, NY-10016.|Department of Chemistry, City University of New York at The College of Staten Island, NY, 10314.
authors.forename: Juliet
authors.initials: J
authors.lastname: Baidoo
authors.affiliation: The Center for Developmental Neuroscience, City University of New York at The College of Staten Island, NY, 10314.
authors.forename: Angela
authors.initials: A
authors.lastname: Fried
authors.affiliation: The Center for Developmental Neuroscience, City University of New York at The College of Staten Island, NY, 10314.
authors.forename: Doaa
authors.initials: D
authors.lastname: Atwi
authors.affiliation: CUNY Doctoral Program In Chemistry, CUNY Graduate Center, NY-10016.
authors.forename: Sukanta
authors.initials: S
authors.lastname: Dolai
authors.affiliation: Karches Center for Oncology Research, Feinstein Institute for Medical Research, NY 11030.|Department of Neurosurgery, Hofstra Northwell School of Medicine, NY 11030.|Department of Otolaryngology, Hofstra Northwell School of Medicine, NY 11030.
authors.forename: John
authors.initials: J
authors.lastname: Boockvar
authors.affiliation: Karches Center for Oncology Research, Feinstein Institute for Medical Research, NY 11030.|Department of Neurosurgery, Hofstra Northwell School of Medicine, NY 11030.|Department of Molecular Medicine, Hofstra Northwell School of Medicine, NY 11030.
authors.forename: Marc
authors.initials: M
authors.lastname: Symons
authors.affiliation: Karches Center for Oncology Research, Feinstein Institute for Medical Research, NY 11030.|Department of Molecular Medicine, Hofstra Northwell School of Medicine, NY 11030.|Department of Radiation Medicine, Hofstra Northwell School of Medicine, NY 11030.
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Ruggieri
authors.affiliation: Department of Chemistry, City University of New York at The College of Staten Island, NY, 10314.
authors.forename: Krishnaswami
authors.initials: K
authors.lastname: Raja
authors.affiliation: CUNY Doctoral Program In Biochemistry, CUNY Graduate Center, NY-10016. probal.banerjee@csi.cuny.edu.|Department of Chemistry, City University of New York at The College of Staten Island, NY, 10314. probal.banerjee@csi.cuny.edu.|The Center for Developmental Neuroscience, City University of New York at The College of Staten Island, NY, 10314. probal.banerjee@csi.cuny.edu.
authors.forename: Probal
authors.initials: P
authors.lastname: Banerjee
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001119:Arginase / Q000378:metabolism; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D045744:Cell Line, Tumor; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D008840:Microfilament Proteins; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000970:Antineoplastic Agents; D001119:Arginase; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D003474:Curcumin; D004268:DNA-Binding Proteins; D008840:Microfilament Proteins; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; D050794:STAT1 Transcription Factor; C112986:AIF1 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: brain tumor; cancer; curcumin; microglia; repolarization