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Anticancer Agents Med Chem. 2019 Jul 21. doi: 10.2174/1871520619666190722101207. [Epub ahead of print]

Hydroxytyrosol and Oleuropein Inhibit Migration and Invasion of MDA-MB-231 Triple-Negative Breast Cancer Cell via Induction of Autophagy.

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Animal, Plant and Food Inspection Center, Nanjing Customs, 39 Chuangzhi Rd., Nanjing 210017. China.
Key Lab of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166. China.



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 is still unclear. This study aimed to explore the molecular mechanisms underlying the antitumor effect of HT and OL in TNBC.


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.


Treatment with HT or OL reduced MDA-MB-231 cell viability in a dose-dependent manner. MDA-MB-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/I and Beclin-1 downregulation and reversing p62 upregulation.


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.


Autophagy; MDA-MB-231; hepatocyte growth factor; hydroxytyrosol; oleuropein; triple-negative breast cancer

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