Cargando…

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

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 ot...

Descripción completa

Detalles Bibliográficos
Autores principales: Mukherjee, Sumit, Baidoo, Juliet N. E., Sampat, Samay, Mancuso, Andrew, David, Lovena, Cohen, Leah S., Zhou, Shuiqin, Banerjee, Probal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017476/
https://www.ncbi.nlm.nih.gov/pubmed/29346317
http://dx.doi.org/10.3390/molecules23010201
_version_ 1783334758716014592
author Mukherjee, Sumit
Baidoo, Juliet N. E.
Sampat, Samay
Mancuso, Andrew
David, Lovena
Cohen, Leah S.
Zhou, Shuiqin
Banerjee, Probal
author_facet Mukherjee, Sumit
Baidoo, Juliet N. E.
Sampat, Samay
Mancuso, Andrew
David, Lovena
Cohen, Leah S.
Zhou, Shuiqin
Banerjee, Probal
author_sort Mukherjee, Sumit
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6017476
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-60174762018-11-13 Liposomal TriCurin, A Synergistic Combination of Curcumin, Epicatechin Gallate and Resveratrol, Repolarizes Tumor-Associated Microglia/Macrophages, and Eliminates Glioblastoma (GBM) and GBM Stem Cells Mukherjee, Sumit Baidoo, Juliet N. E. Sampat, Samay Mancuso, Andrew David, Lovena Cohen, Leah S. Zhou, Shuiqin Banerjee, Probal Molecules Article 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. MDPI 2018-01-18 /pmc/articles/PMC6017476/ /pubmed/29346317 http://dx.doi.org/10.3390/molecules23010201 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mukherjee, Sumit
Baidoo, Juliet N. E.
Sampat, Samay
Mancuso, Andrew
David, Lovena
Cohen, Leah S.
Zhou, Shuiqin
Banerjee, Probal
Liposomal TriCurin, A Synergistic Combination of Curcumin, Epicatechin Gallate and Resveratrol, Repolarizes Tumor-Associated Microglia/Macrophages, and Eliminates Glioblastoma (GBM) and GBM Stem Cells
title Liposomal TriCurin, A Synergistic Combination of Curcumin, Epicatechin Gallate and Resveratrol, Repolarizes Tumor-Associated Microglia/Macrophages, and Eliminates Glioblastoma (GBM) and GBM Stem Cells
title_full Liposomal TriCurin, A Synergistic Combination of Curcumin, Epicatechin Gallate and Resveratrol, Repolarizes Tumor-Associated Microglia/Macrophages, and Eliminates Glioblastoma (GBM) and GBM Stem Cells
title_fullStr Liposomal TriCurin, A Synergistic Combination of Curcumin, Epicatechin Gallate and Resveratrol, Repolarizes Tumor-Associated Microglia/Macrophages, and Eliminates Glioblastoma (GBM) and GBM Stem Cells
title_full_unstemmed Liposomal TriCurin, A Synergistic Combination of Curcumin, Epicatechin Gallate and Resveratrol, Repolarizes Tumor-Associated Microglia/Macrophages, and Eliminates Glioblastoma (GBM) and GBM Stem Cells
title_short Liposomal TriCurin, A Synergistic Combination of Curcumin, Epicatechin Gallate and Resveratrol, Repolarizes Tumor-Associated Microglia/Macrophages, and Eliminates Glioblastoma (GBM) and GBM Stem Cells
title_sort liposomal tricurin, a synergistic combination of curcumin, epicatechin gallate and resveratrol, repolarizes tumor-associated microglia/macrophages, and eliminates glioblastoma (gbm) and gbm stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017476/
https://www.ncbi.nlm.nih.gov/pubmed/29346317
http://dx.doi.org/10.3390/molecules23010201
work_keys_str_mv AT mukherjeesumit liposomaltricurinasynergisticcombinationofcurcuminepicatechingallateandresveratrolrepolarizestumorassociatedmicrogliamacrophagesandeliminatesglioblastomagbmandgbmstemcells
AT baidoojulietne liposomaltricurinasynergisticcombinationofcurcuminepicatechingallateandresveratrolrepolarizestumorassociatedmicrogliamacrophagesandeliminatesglioblastomagbmandgbmstemcells
AT sampatsamay liposomaltricurinasynergisticcombinationofcurcuminepicatechingallateandresveratrolrepolarizestumorassociatedmicrogliamacrophagesandeliminatesglioblastomagbmandgbmstemcells
AT mancusoandrew liposomaltricurinasynergisticcombinationofcurcuminepicatechingallateandresveratrolrepolarizestumorassociatedmicrogliamacrophagesandeliminatesglioblastomagbmandgbmstemcells
AT davidlovena liposomaltricurinasynergisticcombinationofcurcuminepicatechingallateandresveratrolrepolarizestumorassociatedmicrogliamacrophagesandeliminatesglioblastomagbmandgbmstemcells
AT cohenleahs liposomaltricurinasynergisticcombinationofcurcuminepicatechingallateandresveratrolrepolarizestumorassociatedmicrogliamacrophagesandeliminatesglioblastomagbmandgbmstemcells
AT zhoushuiqin liposomaltricurinasynergisticcombinationofcurcuminepicatechingallateandresveratrolrepolarizestumorassociatedmicrogliamacrophagesandeliminatesglioblastomagbmandgbmstemcells
AT banerjeeprobal liposomaltricurinasynergisticcombinationofcurcuminepicatechingallateandresveratrolrepolarizestumorassociatedmicrogliamacrophagesandeliminatesglioblastomagbmandgbmstemcells