Nano-Curcumin Inhibits Proliferation of Esophageal Adenocarcinoma Cells and Enhances the T Cell Mediated Immune Response

Abstract

In Western countries the incidence of the esophageal adenocarcinoma (EAC) has risen at a more rapid rate than that of any other malignancy. Despite intensive therapies this cancer is associated with extreme high morbidity and mortality. For this reason, novel effective therapeutic strategies are urgently required. Dendritic Cell (DC)-based immunotherapy is a promising novel treatment strategy, which combined with other anti-cancer strategies has been proven to be beneficial for cancer patients. Curcumin (diferuloylmethane), is a natural polyphenol that is known for its anti-cancer effects however, in it’s free form, curcumin has poor bioavailability. The aim of this study was to investigate whether using a highly absorptive form of curcumin, dispersed with colloidal nano-particles, named Theracurmin would be more effective against EAC cells and to analyze if this new compound affects DC-induced T cell response. As a result, we show efficient uptake of nano-curcumin by the EAC cell lines, OE33, and OE19. Moreover, nano-curcumin significantly decreased the proliferation of the EAC cells, while did not affect the normal esophageal cell line HET-1A. We also found that nano-curcumin significantly up-regulated the expression of the co-stimulatory molecule CD86 in DCs and significantly decreased the secretion of pro-inflammatory cytokines from in vitro activated T cells. When we combined T cells with nano-curcumin treatment in OE19 and OE33, we found that the basic levels of T cell induced cytotoxicity of 6.4 and 4.1%, increased to 15 and 13%, respectively. In conclusion, we found that nano-curcumin is effective against EAC, sensitizes EAC cells to T cell induced cytotoxicity and decreases the pro-inflammatory signals from T cells. Combining DC immunotherapy with nano-curcumin is potentially a promising approach for future treatment of EAC.

Anticancer potential of naturally occurring immunoepigenetic modulators: A promising avenue?

“…In agreement with these results, curcumin suppresses metastatic breast cancer in mice by increasing M1 and decreasing M2 macrophage populations in the TME, resulting in decreased STAT3, IL‐10, and arginase I gene expression and secretion . Another study revealed that curcumin nanoparticles upregulate the expression of the costimulatory molecule CD86 in DCs and decrease the secretion of proinflammatory cytokines (IL‐1β, IL‐6, IL‐8, IL‐10, and tumor necrosis factor α [TNF‐α]) from activated T cells, leading to their enhanced cytolytic ability against esophageal adenocarcinoma cells . Finally, curcumin, in combination with adoptive T‐cell therapy, restrains tumor growth and extends the survival of melanoma xenografted mice by enhancing the cytotoxicity of CTLs against tumor cells.…”

“…68 Another study revealed that curcumin nanoparticles upregulate the expression of the costimulatory molecule CD86 in DCs and decrease the secretion of proinflammatory cytokines (IL-1β, IL-6, IL-8, IL-10, and tumor necrosis factor α [TNF-α]) from activated T cells, leading to their enhanced cytolytic ability against esophageal adenocarcinoma cells. 69 Finally, curcumin, in combination with adoptive T-cell therapy, restrains tumor growth and extends the survival of melanoma xenografted mice by enhancing the cytotoxicity of CTLs against tumor cells. It is noteworthy that the enhanced antitumor response elicited by curcumin, other than a depletion of Tregs and TGF-β secretion, was caused by the downregulation of IDO expression in melanoma cells.…”

Potential amelioration of nicotine‐induced toxicity by nanocurcumin

“…According to them, the nanoformulation does not result in lung accumulation and thus increases overall systemic curcumin exposure. Nanocurcumin also inhibits proliferation of esophageal adenocarcinoma cells and enhances the T cell mediated immune response (Milano et al, ). Our study also suggests that nanocurcumin more effectively ameliorates nicotine‐induced toxicities through normalizing the function of the hepato‐functional enzymes, kidney function parameters, lipid profiles, anti‐oxidant status, and maintaining the structural integrity of different tissues under nicotine stress condition.…”

Inhibitory effects of maslinic acid upon human esophagus, stomach and pancreatic cancer cells

“…However, it is unknown that MA could retard the growth of other GI tract cancer cells such as esophagus, stomach or pancreatic cancer cells. Human esophageal squamous cancer cell line, OE33; gastric cancer cell line, SGC-7901; and pancreatic cancer cell line, Panc-1, have been widely used for anti-cancer studies to investigate the apoptotic effects and possible mechanisms of certain compounds (Li et al, 2012;Milano et al, 2013;Zhang et al, 2013). In our present study, these cancer cell lines were used as representative cell lines for esophageal cancer, gastric cancer and pancreatic cancer, respectively, to evaluate the potential of MA as an anti-GI tract cancer agent.…”