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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

Caspase-3 induction in MP2 cells is potentiated by curcuminoids with ω-3 and anti-oxidants. Replicate MP2 cell cultures (N = 3) in 24-well plates were treated 24 h with curcuminoids in Smartfish emulsion or fish oil, the cells were harvested and caspase-3 was assayed in the whole lysate. The experiment was repeated twice with comparable results. The maximal induction of caspase-3 reached by 10 μM curcuminoids in Smartfish was greater than any other treatment (P < 0.0001).
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Figure 1: Caspase-3 induction in MP2 cells is potentiated by curcuminoids with ω-3 and anti-oxidants. Replicate MP2 cell cultures (N = 3) in 24-well plates were treated 24 h with curcuminoids in Smartfish emulsion or fish oil, the cells were harvested and caspase-3 was assayed in the whole lysate. The experiment was repeated twice with comparable results. The maximal induction of caspase-3 reached by 10 μM curcuminoids in Smartfish was greater than any other treatment (P < 0.0001).

Mentions: We tested apoptosis induction using the enzyme assay for the executioner caspase-3 expression. In MP2 cells alone, caspase-3 expression was low (1.2 μM) and was not significantly increased by curcuminoids (1 μM) alone or with ω-3 and anti-oxidants, or by fish oil; methanol is used as a control However, curcuminoids (10 μM) emulsified in ω-3 and anti-oxidants induced robust capase-3 expression, which was significantly higher (P < 0.0001) than that induced by curcuminoids (10 μM) in fish oil (Figure 1).


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)

Caspase-3 induction in MP2 cells is potentiated by curcuminoids with ω-3 and anti-oxidants. Replicate MP2 cell cultures (N = 3) in 24-well plates were treated 24 h with curcuminoids in Smartfish emulsion or fish oil, the cells were harvested and caspase-3 was assayed in the whole lysate. The experiment was repeated twice with comparable results. The maximal induction of caspase-3 reached by 10 μM curcuminoids in Smartfish was greater than any other treatment (P < 0.0001).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Caspase-3 induction in MP2 cells is potentiated by curcuminoids with ω-3 and anti-oxidants. Replicate MP2 cell cultures (N = 3) in 24-well plates were treated 24 h with curcuminoids in Smartfish emulsion or fish oil, the cells were harvested and caspase-3 was assayed in the whole lysate. The experiment was repeated twice with comparable results. The maximal induction of caspase-3 reached by 10 μM curcuminoids in Smartfish was greater than any other treatment (P < 0.0001).
Mentions: We tested apoptosis induction using the enzyme assay for the executioner caspase-3 expression. In MP2 cells alone, caspase-3 expression was low (1.2 μM) and was not significantly increased by curcuminoids (1 μM) alone or with ω-3 and anti-oxidants, or by fish oil; methanol is used as a control However, curcuminoids (10 μM) emulsified in ω-3 and anti-oxidants induced robust capase-3 expression, which was significantly higher (P < 0.0001) than that induced by curcuminoids (10 μM) in fish oil (Figure 1).

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