Background: Breast Cancer (BC) is the leading cause of cancer-related deaths among women. As
such, novel chemotherapeutic agents are urgently needed, especially for Triple-Negative Breast Cancer (TNBC).
Hydroxytyrosol (HT) and Oleuropein (OL) are rich in olive oil, which is associated with a low occurrence of
BC. However, the effects and mechanisms of action of HT and OL in BC cells are still unclear. This study
aimed to explore the molecular mechanisms underlying the antitumor effect of HT and OL in TNBC.
Methods: TNBC MDA-MB-231 cells were treated with HT and OL in combination with Hepatocyte Growth
Factor (HGF), rapamycin (Rapa, an inducer of autophagy) or 3-methyladenine (3-MA, an inhibitor of autophagy).
Cell viability, migration, invasion, and autophagy signaling were analyzed by scratch assays, transwell
migration assays, and Western blot analysis.
Results: Treatment with HT or OL reduced MDA-MB-231 cell viability in a dose-dependent manner. MDAMB-
231 cells were more sensitive to HT treatment than OL treatment. Rapa treatment could significantly block
HGF-induced MDA-MB-231 cell migration and invasion, suggesting that inhibition of autophagy could promote
migration and invasion. Moreover, HT or OL treatment significantly suppressed HGF or 3-MA induced cell
migration and invasion by reversing LC3-II/LC3-I and Beclin-1 downregulation and reversing p62 upregulation.
Conclusion: These data indicated that HT and OL may inhibit migration and invasion of TNBC cells by activating
autophagy. These findings provide potential therapeutic strategies that target autophagy to limit the pathogenesis
and progression of BC.