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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

Curcuminoid blockade of interferon-γ production is reduced by removal of curcumin (A) after 2 days, (B) after 6 days. Triplicate MP2 cell cultures in 24-well plates were cultured with or without Smartfish emulsion and curcuminoids or with DMEM, washed and replaced with the indicated medium and NK cells for 24 or 48 h. Note that the inhibition of IFN-γ by curcuminoids was reduced by washing MP2 cells.
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Figure 6: Curcuminoid blockade of interferon-γ production is reduced by removal of curcumin (A) after 2 days, (B) after 6 days. Triplicate MP2 cell cultures in 24-well plates were cultured with or without Smartfish emulsion and curcuminoids or with DMEM, washed and replaced with the indicated medium and NK cells for 24 or 48 h. Note that the inhibition of IFN-γ by curcuminoids was reduced by washing MP2 cells.

Mentions: We tested the effect on IFN-γ production of incubation of the cells in a curcuminoid-free medium after addition of NK cells. The curcuminoid-free interval after addition of NK cells resulted in the following mean IFN-γ levels: (a) co culture of NK and cancer cells without curcuminoids for 48 h: 201 pg/ml; (b) co culture without curcuminoids for 24 h: 90 pg/ml; (c) co culture with constant presence of curcuminoids for 48 h: 27 pg/ml (Figure 6A). When the experiment was increased to 96 h, the reduction in inhibition was still observed (Figure 6B).


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)

Curcuminoid blockade of interferon-γ production is reduced by removal of curcumin (A) after 2 days, (B) after 6 days. Triplicate MP2 cell cultures in 24-well plates were cultured with or without Smartfish emulsion and curcuminoids or with DMEM, washed and replaced with the indicated medium and NK cells for 24 or 48 h. Note that the inhibition of IFN-γ by curcuminoids was reduced by washing MP2 cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Curcuminoid blockade of interferon-γ production is reduced by removal of curcumin (A) after 2 days, (B) after 6 days. Triplicate MP2 cell cultures in 24-well plates were cultured with or without Smartfish emulsion and curcuminoids or with DMEM, washed and replaced with the indicated medium and NK cells for 24 or 48 h. Note that the inhibition of IFN-γ by curcuminoids was reduced by washing MP2 cells.
Mentions: We tested the effect on IFN-γ production of incubation of the cells in a curcuminoid-free medium after addition of NK cells. The curcuminoid-free interval after addition of NK cells resulted in the following mean IFN-γ levels: (a) co culture of NK and cancer cells without curcuminoids for 48 h: 201 pg/ml; (b) co culture without curcuminoids for 24 h: 90 pg/ml; (c) co culture with constant presence of curcuminoids for 48 h: 27 pg/ml (Figure 6A). When the experiment was increased to 96 h, the reduction in inhibition was still observed (Figure 6B).

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