Using curcumin to turn the innate immune system against cancer.

Curcumin has been at the center of vigorous research and major debate during the past decade. Inspired by its anti-inflammatory properties, many curcumin-based products are being sold now to manage various forms of arthritis. Parallel preclinical studies have established its role in dissolving beta-amyloid plaques, tau-based neurofibrillary tangles, and also alpha-synuclein-linked protein aggregates typically observed in Parkinson's disease.

Phytosomal curcumin causes natural killer cell-dependent repolarization of glioblastoma (GBM) tumor-associated microglia/macrophages and elimination of GBM and GBM stem cells.

Background: Glioblastoma (GBM) is a primary brain tumor with a 5-year survival rate of ≤5%. We have shown earlier that GBM-antibody-linked curcumin (CC) and also phytosomal curcumin (CCP) rescue 50-60% of GBM-bearing mice while repolarizing the tumor-associated microglia/macrophages (TAM) from the tumor-promoting M2-type to the tumoricidal M1-type. However, systemic application of CCP yields only sub-IC50 concentrations of CC in the plasma, which is unlikely to kill GBM cells directly.

TriCurin, a synergistic formulation of curcumin, resveratrol, and epicatechin gallate, repolarizes tumor-associated macrophages and triggers an immune response to cause suppression of HPV+ tumors.

Our earlier studies reported a unique potentiated combination (TriCurin) of curcumin (C) with two other polyphenols. The TriCurin-associated C displays an IC50 in the low micromolar range for cultured HPV+ TC-1 cells. In contrast, because of rapid degradation in vivo, the TriCurin-associated C reaches only low nano-molar concentrations in the plasma, which are sub-lethal to tumor cells.

Curcumin changes the polarity of tumor-associated microglia and eliminates glioblastoma.

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.