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Molecules 2018, 23(1), 201; https://doi.org/10.3390/molecules23010201

Liposomal TriCurin, A Synergistic Combination of Curcumin, Epicatechin Gallate and Resveratrol, Repolarizes Tumor-Associated Microglia/Macrophages, and Eliminates Glioblastoma (GBM) and GBM Stem Cells

1
Ph.D. Program in Biochemistry, The Graduate Center, City University of New York, New York, NY 10016, USA
2
Department of Chemistry, City University of New York, The College of Staten Island, Staten Island, NY 10314, USA
3
College of Arts and Science, New York University, New York, NY 10003, USA
4
Center for Developmental Neuroscience, City University of New York, The College of Staten Island, Staten Island, NY 10314, USA
*
Author to whom correspondence should be addressed.
Received: 20 November 2017 / Revised: 3 January 2018 / Accepted: 15 January 2018 / Published: 18 January 2018
(This article belongs to the Special Issue Catechin in Human Health and Disease)
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Abstract

Glioblastoma (GBM) is a deadly brain tumor with a current mean survival of 12–15 months. Despite being a potent anti-cancer agent, the turmeric ingredient curcumin (C) has limited anti-tumor efficacy in vivo due to its low bioavailability. We have reported earlier a strategy involving the use two other polyphenols, epicatechin gallate (E) from green tea and resveratrol (R) from red grapes at a unique, synergistic molar ratio with C (C:E:R: 4:1:12.5, termed TriCurin) to achieve superior potency against HPV+ tumors than C alone at C:E:R (μM): 32:8:100 (termed 32 μM+ TriCurin). We have now prepared liposomal TriCurin (TrLp) and demonstrated that TrLp boosts activated p53 in cultured GL261 mouse GBM cells to trigger apoptosis of GBM and GBM stem cells in vitro. TrLp administration into mice yielded a stable plasma concentration of 210 nM C for 60 min, which, though sub-lethal for cultured GL261 cells, was able to cause repolarization of M2-like tumor (GBM)-associated microglia/macrophages to the tumoricidal M1-like phenotype and intra-GBM recruitment of activated natural killer cells. The intratumor presence of such tumoricidal immune cells was associated with concomitant suppression of tumor-load, and apoptosis of GBM and GBM stem cells. Thus, TrLp is a potential onco-immunotherapeutic agent against GBM tumors. View Full-Text
Keywords: curcumin; epicatechin gallate; resveratrol; TriCurin; liposomes; glioblastoma multiforme (GBM); GBM stem cells; tumor-associated microglia/macrophages (TAM); NK cells curcumin; epicatechin gallate; resveratrol; TriCurin; liposomes; glioblastoma multiforme (GBM); GBM stem cells; tumor-associated microglia/macrophages (TAM); NK cells
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Mukherjee, S.; Baidoo, J.N.E.; Sampat, S.; Mancuso, A.; David, L.; Cohen, L.S.; Zhou, S.; Banerjee, P. Liposomal TriCurin, A Synergistic Combination of Curcumin, Epicatechin Gallate and Resveratrol, Repolarizes Tumor-Associated Microglia/Macrophages, and Eliminates Glioblastoma (GBM) and GBM Stem Cells. Molecules 2018, 23, 201.

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