Oleuropein inhibits invasion of squamous cell carcinoma of the head and neck through TGF-β1 signaling pathway

Abstract

Background Squamous cell carcinoma of the head and neck (SCCHN) is globally the sixth most common cancer. TGF-β1 is a key regulator of cell proliferation and differentiation, and it induces the epithelial-mesenchymal transition (EMT) by activating Smad2 signaling in SCCHN cells. Previous studies have revealed that oleuropein (OL) can inhibit the EMT alterations and migration of cancer cells. The aim of this study was to examine the involvement of TGF-β1 signaling pathway in SCCHN and the effect of OL on it. Methods Through in vitro experiments at cellular level and in vivo evaluation in mouse xenograft tumor model, with morphological and Western blotting assays, we examined the effects of OL on TGF-β1-mediated signaling pathway in Tu686, CAL-27 and 686LN-M2 tumor cell lines. Results We found that OL reversed the TGF-β1-induced EMT, and changed the morphology of cells and the expression levels of epithelial and interstitial markers. Wound-healing and transwell invasion assays indicated that OL reversed the TGF-β1-promoted cell migration and invasion dramatically. The effects of OL were also verified in xenograft tumor model of mice, and the findings were identical to the in vitro assays. Conclusion This study demonstrated that OL inhibits the growth and metastasis of SCCHN by interfering with the TGF-β1 signaling pathway, and the findings are beneficial for the development of prevention and treatment strategy of SCCHN. Due to the low toxicity and less side effects, OL may be of potential value in the inhibition of metastasis of SCCHN and improve survival.

Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine

“…Treatment of human cell lines Tu686 and CAL-27 with 50–200 μg/mL OLE (≈92.5–370 μM) significantly reduced cell viability, while no effect was elicited by concentrations ≤ 25 μg/mL (≈46 μM). Consistently, 25 μg/mL did not change the apoptotic rate in the mentioned cell lines, but inhibited epithelial-to-mesenchymal transition (EMT) induced by transforming growth factor-β1 TGF-β1 [ 96 , 229 ]. The effects of OLE on EMT-related proteins were also verified in a in vivo model of 686LN-M2 cell line xenograft in BALB/c nude mice [ 96 ].…”

“…Consistently, 25 μg/mL did not change the apoptotic rate in the mentioned cell lines, but inhibited epithelial-to-mesenchymal transition (EMT) induced by transforming growth factor-β1 TGF-β1 [ 96 , 229 ]. The effects of OLE on EMT-related proteins were also verified in a in vivo model of 686LN-M2 cell line xenograft in BALB/c nude mice [ 96 ].…”