Furowanin A Exhibits Anti-proliferative and Pro-apoptotic Activities by Targeting Sphingosine Kinase 1 in Osteosarcoma.

This study is designed to evaluate the efficacy of Fur A against OS. The effect of Fur A on cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. Western blotting and quantitative real-time PCR (qRT-PCR) were performed to determine the protein and mRNA level of sphingosine kinase 1 (SphK1), respectively. To validate the role of SphK1 in the pro-apoptotic activity of Fur A, overexpressing SphK1 vector and siRNA targeting SphK1 were utilized to transfect OS cells. Moreover, a OS xenograft murine model was used to analyze the therapeutic efficacy of Fur A in vivo. Fur A treatment led to a dose-dependent decrease in the number of viable cells. It also exhibited anti-proliferative activity and significantly promoted apoptotic cell death in OS cell lines. Our results showed that the anti-cancer activity of Fur A was associated with downregulation of SphK1 and inactivation of its downstream signaling. The mediatory role of SphK1 was validated when the pro-apoptotic activity of Fur A was significantly blocked by SphK1 overexpression, while SphK1 knockdown sensitized the OS cells to Fur A. We concluded that Fur A can exhibit anti-growth and pro-apoptotic activities in vitro and in vivo in OS by downregulating SphK1. Our study highlights the possibility of utilizing Fur A as a chemotherapeutic agent in the treatment of OS. This article is protected by copyright. All rights reserved. PMID: 31197942 [PubMed - as supplied by publisher]
Source: Anatomical Record - Category: Anatomy Authors: Tags: Anat Rec (Hoboken) Source Type: research