Atractylon inhibits the tumorigenesis of glioblastoma through SIRT3 signaling.

ABSTRACT

Glioblastoma (GBM) is the most common primary malignant brain tumor. Although there are various treatments for glioblastoma including surgery, radiotherapy, systemic therapy (chemotherapy and targeted therapy) and supportive therapy, the overall prognosis remains poor and the long-term survival rate is very low. Atractylon, a bioactive compound extracted from the Chinese herb Atractylodes lancea (Thunb.) DC. or Atractylodes chinensis (DC.) Koidz., has been reported to induce apoptosis and suppress metastasis in hepatic cancer cells. However, the roles and mechanisms of atractylon in GBM cells remain unknown. In the present study, we aimed to evaluate the effects of atractylon on the anti-tumorigenesis properties of GBM. Firstly, results of CCK8, colony formation, cell proliferation, and flow cytometry assays showed that atractylon inhibited the proliferation of GBM cells by arresting cells at the G1 phase of cell cycle. In addition, atractylon suppressed the migration and induced apoptosis of GBM cells. Mechanistically, atractylon treatment caused a significant up-regulation of sirtuin 3 (SIRT3, a tumor suppressor) mRNA and protein in GBM cells. Furthermore, inhibition of SIRT3 by the selective SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP) partially restored the anti-proliferation and migration effects of atractylon in GBM cells. Finally, atractylon treatment also inhibited the in vivo growth of GBM cells in xenograft models through SIRT3 activation. Taken together, these results reveal a previously unknown role of atractylon in inhibiting GBM in vitro and in vivo through up-regulating SIRT3, which suggests novel strategies for the treatment of GBM.