(P13-006-23) Oleic Acid-Induced Oxidative Stress Reduces Migration and Invasion of Stem Cell-Like Breast Cancer Cells

Objectives: Oleic acid, a monounsaturated fatty acid found in a variety of plant sources, including olives, almonds and avocados, provides beneficial health effects such as cardiovascular disease improvement, anti-inflammatory and anti-cancer properties. However, studies on the anticancer effect and mechanism of oleic acid on cancer stem cells resistant to conventional treatments are extremely limited. We evaluated the ability of oleic acid against stem cell-like breast cancer cells.

Methods: Mammosphere assay was performed to provide an estimate of the number of cells with cancer-causing capacity in a heterogeneous tumor cell population. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and clonogenic assay were assessed to evaluate cell viability. Flow cytometry (FACS) was used to characterize CD44+/CD24- expressing cells and intracellular reactive oxygen species (ROS) levels. To determine gene and protein expression, it was confirmed through quantitative real time polymerase chain reaction and western blot, respectively.

Results: The stemness properties of stem cell-like breast cancer cells were reduced by oleic acid. Oleic acid attenuated the growth of stem cell-like breast cancer cells with low ROS by inducing oxidative stress in a time- and concentration-dependent manner. It also reduced the activity of the antioxidant enzyme GPx1-dependent FAK-AKT axis. In particular, inhibition of translocation of NF-κB, a transcriptional regulator in the downstream signaling pathway of AKT, from the cytoplasm to the nucleus limited the migration and invasion capabilities of stem cell-like breast cancer cells. These results were completely overcome by treatment with the antioxidant NAC, and we show that the induction of oxidative stress by oleic acid plays an important role in targeting stem cell-like breast cancer cells.

Conclusions: Our results provide evidence that oleic acid can suppress cancer stem cells that are resistant to conventional therapies and induce tumor metastasis. It also suggests that oleic acid, which is abundant in Mediterranean diet foods, can be a potential treatment targeting breast cancer.

Funding Sources: This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education.