A Synergistic Antiproliferation Effect of Docosahexaenoic Acid and Curcumin in Breast Cancer Cells.

Effects of the Docosahexaenoic acid (DHA)+ curcumin (CCM) combination on cell proliferation were evaluated using varying concentrations, at a fixed ratio, of DHA and CCM based on their individual ED50. Detection of synergy was performed using nonlinear regression of a sigmoid dose response model and Combination Index approaches. Cell molecular network responses were investigated through whole genome microarray analysis of transcript level changes. DHA and CCM had an antiproliferative effect in SKBR3, MDA‐MB‐231, MDA‐MB‐361, MCF7 and MCF10AT cells; the effect was synergistic for SKBR3 (ER − PR − HER2 + ) relative to the two compounds individually. Transcript‐level responses to CCM+DHA, in disease‐relevant functional categories, were largely non‐overlapping with changes caused by CCM or DHA individually. Cellular pools of PPARγ and phospho‐p53 were increased by CCM+DHA relative to either compound alone. DHA enhanced cellular uptake of CCM, variably across cell lines. The transcriptomic data show that among several signaling events that are uniquely affected by the combined presence of DHA and CCM, CYP450 and SERPINB5‐mediated pathways play an important role in the synergistic antiproliferation effects. The combination of DHA and CCM is potentially a dietary supplemental treatment for some breast cancers, likely dependent upon molecular phenotype. Funding: RO3CA137765