1, 6-O, O-Diacetylbritannilactone from Inula britannica Induces Anti-Tumor Effect on Oral Squamous Cell Carcinoma via miR-1247-3p/LXRα/ABCA1 Signaling

Introduction: Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy affecting the oral cavity and is associated with severe morbidity and high mortality. 1, 6-O, O-Diacetylbritannilactone (OODBL) isolated from the medicinal herb of Inula britannica has various biological activities such as anti-inflammation and anti-cancer. However, the effect of OODBL on OSCC progression remains unclear. Here, we were interested in the function of OODBL in the development of OSCC.

Methods: The effect of OODBL on OSCC progression was analyzed by MTT assays, colony formation assays, transwell assays, apoptosis analysis, cell cycle analysis, and in vivo tumorigenicity analysis. The mechanism investigation was performed by qPCR assays, Western blot analysis, and luciferase reporter gene assays.

Results: We found that OODBL inhibits the proliferation of OSCC cells in vitro. Moreover, the migration and invasion were attenuated by OODBL treatment in the OSCC cells. OODBL arrested cells at the G0/G1 phase and induced cell apoptosis. OODBL was able to up-regulate the expression of LXRα, ABCA1, and ABCG1 in the system. In addition, OODBL activated LXRα/ABCA1 signaling by targeting miR-1247-3p. Furthermore, the expression levels of cytochrome c in the cytoplasm, cleaved caspase-9, and cleaved caspase-3 were dose-dependently reduced by OODBL. Besides, OODBL increased the expression ratio of Bax to Bcl-2. Moreover, OODBL repressed tumor growth of OSCC cells in vivo.

Discussion: Thus, we conclude that OODBL inhibits OSCC progression by modulating miR-1247-3p/LXRα/ABCA1 signaling. Our finding provides new insights into the mechanism by which OODBL exerts potent anti-tumor activity against OSCC. OODBL may be a potential anti-tumor candidate, providing a novel clinical treatment strategy of OSCC.

Keywords: LXRα/ABCA1 signaling; OODBL; OSCC; anti-tumor; miR-1247-3p.