Abstract 5251: Amentoflavone regulate Hh-Gli1 signaling pathway and inhibits tumorsphere formation in U251 glioblastoma cells

Cancer stem cells represent a rare population of cells with a self-renewal capacity, and potentially are involved in tumor progression, tumor relapse, and resistance to cancer chemotherapies. In this study, we investigated the effect of an active ingredient of chamaecyaris obtuse, amentoflavone, on stemness of U251 glioblastoma cells. We first found that amentoflavone from 1 to10 μM suppressed tumorsphere formation and inhibited the expression of glioblastoma stem cell markers CD133 and ALDH1 in a dose dependent manner. In addition, amentoflavone significantly reduced the expression of Nanog involved in cancer stem cells maintenance in tumorsphere culture. As an upstream modulator, Hedgehog (Hh) signaling mediator Gli1 was confirmed to be highly expressed in tumorsphere culture where the suppression of Gli1 by the treatment of Hh inhibitors (vismodegib and GANT 61) or Gli1-siRNA significantly suppressed the expression of stem cell markers CD133, ALDH1, and Nanog as well as tumorsphere formation in U251 glioblastoma cells. These results indicate that Hh signaling plays an important role in maintaining tumorsphere and stemness of U251 glioblastoma cells. Next, we also found that the treatment of amentoflavone from 1 to10 μM inhibited the expression of Gli1 and its downstream mediator Nanog in tumorsphere culture of U251 glioblastoma cells. Taken together, amentoflavone significantly suppressed Hh/Gli1 signaling which results in inhibition of stemness of U251 glioblastoma cells. Citation Format: Jing Chen, Cheng Bao, Hong Jin Lee. Amentoflavone regulate Hh-Gli1 signaling pathway and inhibits tumorsphere formation in U251 glioblastoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5251. doi:10.1158/1538-7445.AM2017-5251