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Curcuminoids and ω-3 fatty acids with anti-oxidants potentiate cytotoxicity of natural killer cells against pancreatic ductal adenocarcinoma cells and inhibit interferon γ production.

Halder RC, Almasi A, Sagong B, Leung J, Jewett A, Fiala M - Front Physiol (2015)

Bottom Line: We tested curcuminoids in an emulsion of ω-3 fatty acids and anti-oxidants ("Smartfish") regarding their direct cytocidal effect and enhancement of the cytocidal activity of NK cells in pancreatic ductal adenocarcinoma (PDAC) cells (Mia Paca 2 and L3.6).Importantly, curcuminoids with ω-3 fatty acids and anti-oxidants or with RvD1 significantly potentiated NK cell cytocidal function and protected them against degradation.In conclusion, curcuminoids with ω-3 fatty acids and anti-oxidants or with RvD1 have increased cytotoxic activity on PDAC cells alone and with NK cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, University of California, Los Angeles, School of Medicine Los Angeles, CA, USA.

ABSTRACT
Pancreatic cancer has a poor prognosis attributed in part to immune suppression and deactivation of natural killer (NK) cells. Curcuminoids have a potential for improving the therapy of pancreatic cancer given promising results in cancer models and a clinical trial, but their oral absorption is limited. Our objective in this study is to show curcuminoid anti-oncogenic effects alone and together with human NK cells. We tested curcuminoids in an emulsion of ω-3 fatty acids and anti-oxidants ("Smartfish") regarding their direct cytocidal effect and enhancement of the cytocidal activity of NK cells in pancreatic ductal adenocarcinoma (PDAC) cells (Mia Paca 2 and L3.6). Curcuminoids (at ≥10 μM) with ω-3 fatty acids and anti-oxidants or with the lipidic mediator resolvin D1 (RvD1) (26 nM) induced high caspase-3 activity in PDAC cells. Importantly, curcuminoids with ω-3 fatty acids and anti-oxidants or with RvD1 significantly potentiated NK cell cytocidal function and protected them against degradation. In a co-culture of cancer cells with NK cells, interferon-γ (IFN-γ) production by NK cells was not altered by ω-3 fatty acids with anti-oxidants or by RvD1 but was inhibited by curcuminoids. The inhibition was not eliminated by ω-3 fatty acids or RvD1 but was relieved by removing curcuminoids after adding NK cells. In conclusion, curcuminoids with ω-3 fatty acids and anti-oxidants or with RvD1 have increased cytotoxic activity on PDAC cells alone and with NK cells. The effects of curcuminoids with ω-3 fatty acids and anti-oxidants on pancreatic cancer will be investigated in a mouse model with humanized immune system.

No MeSH data available.


Related in: MedlinePlus

Active caspase-3 expression in MP2 cancer cells is potentiated by curcuminoids and ω-3 or Resolvin D1. The MP2 cells were stained by phalloidin (green) and by rabbit antibody to active caspase-3/anti-rabbit ALEXA568 (red). (A) Untreated MP2 cells; (B) MP2 cells treated by ω-3 with anti-oxidants (Smartfish); (C) MP2 cells treated by curcuminoids with ω-3 and anti-oxidants (Smartfish); (D) MP2 cells treated by RvD1 and ω-3 with anti-oxidants(Smartfish); (E) MP2 cells treated by fish-oil; (F) MP-2 cells treated by curcuminoids in fish oil. Note the highest expression of caspase-3 in (C,D).
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Figure 2: Active caspase-3 expression in MP2 cancer cells is potentiated by curcuminoids and ω-3 or Resolvin D1. The MP2 cells were stained by phalloidin (green) and by rabbit antibody to active caspase-3/anti-rabbit ALEXA568 (red). (A) Untreated MP2 cells; (B) MP2 cells treated by ω-3 with anti-oxidants (Smartfish); (C) MP2 cells treated by curcuminoids with ω-3 and anti-oxidants (Smartfish); (D) MP2 cells treated by RvD1 and ω-3 with anti-oxidants(Smartfish); (E) MP2 cells treated by fish-oil; (F) MP-2 cells treated by curcuminoids in fish oil. Note the highest expression of caspase-3 in (C,D).

Mentions: We examined apoptosis by immunofluorescence microscopy of caspase-3 antibody stained cells (Figure 2). As shown in integrated optical density (IOD) of red per cell, caspase-3 expression was not observed in untreated MP2 cells (IOD Red/Cell = 21.29), but was seen at a low level in MP2 cells treated with ω-3 and anti-oxidants (IOD Red/Cell = 49.87), and at a high level in MP-2 cells treated with curcuminoids or RvD1 emulsified in ω-3 with anti-oxidants (IOD Red/Cell = 257.01 and 227.55, respectively). The cancer cells treated by ω-3 and anti-oxidants became rounded, detached and some displayed pyknotic nuclei confirming their apoptosis. The emulsification of curcuminoids in fish oil was clearly inferior in the production of apoptosis (IOD Red/Cell = 159.74). Comparable results were obtained in three experiments.


Curcuminoids and ω-3 fatty acids with anti-oxidants potentiate cytotoxicity of natural killer cells against pancreatic ductal adenocarcinoma cells and inhibit interferon γ production.

Halder RC, Almasi A, Sagong B, Leung J, Jewett A, Fiala M - Front Physiol (2015)

Active caspase-3 expression in MP2 cancer cells is potentiated by curcuminoids and ω-3 or Resolvin D1. The MP2 cells were stained by phalloidin (green) and by rabbit antibody to active caspase-3/anti-rabbit ALEXA568 (red). (A) Untreated MP2 cells; (B) MP2 cells treated by ω-3 with anti-oxidants (Smartfish); (C) MP2 cells treated by curcuminoids with ω-3 and anti-oxidants (Smartfish); (D) MP2 cells treated by RvD1 and ω-3 with anti-oxidants(Smartfish); (E) MP2 cells treated by fish-oil; (F) MP-2 cells treated by curcuminoids in fish oil. Note the highest expression of caspase-3 in (C,D).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4440907&req=5

Figure 2: Active caspase-3 expression in MP2 cancer cells is potentiated by curcuminoids and ω-3 or Resolvin D1. The MP2 cells were stained by phalloidin (green) and by rabbit antibody to active caspase-3/anti-rabbit ALEXA568 (red). (A) Untreated MP2 cells; (B) MP2 cells treated by ω-3 with anti-oxidants (Smartfish); (C) MP2 cells treated by curcuminoids with ω-3 and anti-oxidants (Smartfish); (D) MP2 cells treated by RvD1 and ω-3 with anti-oxidants(Smartfish); (E) MP2 cells treated by fish-oil; (F) MP-2 cells treated by curcuminoids in fish oil. Note the highest expression of caspase-3 in (C,D).
Mentions: We examined apoptosis by immunofluorescence microscopy of caspase-3 antibody stained cells (Figure 2). As shown in integrated optical density (IOD) of red per cell, caspase-3 expression was not observed in untreated MP2 cells (IOD Red/Cell = 21.29), but was seen at a low level in MP2 cells treated with ω-3 and anti-oxidants (IOD Red/Cell = 49.87), and at a high level in MP-2 cells treated with curcuminoids or RvD1 emulsified in ω-3 with anti-oxidants (IOD Red/Cell = 257.01 and 227.55, respectively). The cancer cells treated by ω-3 and anti-oxidants became rounded, detached and some displayed pyknotic nuclei confirming their apoptosis. The emulsification of curcuminoids in fish oil was clearly inferior in the production of apoptosis (IOD Red/Cell = 159.74). Comparable results were obtained in three experiments.

Bottom Line: We tested curcuminoids in an emulsion of ω-3 fatty acids and anti-oxidants ("Smartfish") regarding their direct cytocidal effect and enhancement of the cytocidal activity of NK cells in pancreatic ductal adenocarcinoma (PDAC) cells (Mia Paca 2 and L3.6).Importantly, curcuminoids with ω-3 fatty acids and anti-oxidants or with RvD1 significantly potentiated NK cell cytocidal function and protected them against degradation.In conclusion, curcuminoids with ω-3 fatty acids and anti-oxidants or with RvD1 have increased cytotoxic activity on PDAC cells alone and with NK cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, University of California, Los Angeles, School of Medicine Los Angeles, CA, USA.

ABSTRACT
Pancreatic cancer has a poor prognosis attributed in part to immune suppression and deactivation of natural killer (NK) cells. Curcuminoids have a potential for improving the therapy of pancreatic cancer given promising results in cancer models and a clinical trial, but their oral absorption is limited. Our objective in this study is to show curcuminoid anti-oncogenic effects alone and together with human NK cells. We tested curcuminoids in an emulsion of ω-3 fatty acids and anti-oxidants ("Smartfish") regarding their direct cytocidal effect and enhancement of the cytocidal activity of NK cells in pancreatic ductal adenocarcinoma (PDAC) cells (Mia Paca 2 and L3.6). Curcuminoids (at ≥10 μM) with ω-3 fatty acids and anti-oxidants or with the lipidic mediator resolvin D1 (RvD1) (26 nM) induced high caspase-3 activity in PDAC cells. Importantly, curcuminoids with ω-3 fatty acids and anti-oxidants or with RvD1 significantly potentiated NK cell cytocidal function and protected them against degradation. In a co-culture of cancer cells with NK cells, interferon-γ (IFN-γ) production by NK cells was not altered by ω-3 fatty acids with anti-oxidants or by RvD1 but was inhibited by curcuminoids. The inhibition was not eliminated by ω-3 fatty acids or RvD1 but was relieved by removing curcuminoids after adding NK cells. In conclusion, curcuminoids with ω-3 fatty acids and anti-oxidants or with RvD1 have increased cytotoxic activity on PDAC cells alone and with NK cells. The effects of curcuminoids with ω-3 fatty acids and anti-oxidants on pancreatic cancer will be investigated in a mouse model with humanized immune system.

No MeSH data available.


Related in: MedlinePlus