Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 153, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2022.113416
Keywords
Fraxinellone; Glioblastoma; Proliferation; Migration; Apoptosis; Senescence; SIRT3
Funding
- National Natural Science Foundation [92049104, 82071230]
- Scientific Research Foundation for Scholars of HZNU [4125C5021920453, 4125C50220204109]
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Fraxinellone was found to inhibit the proliferation and growth of GBM cells in vitro, as well as suppress their migration and induce apoptosis. The mechanism of action involved the downregulation of SIRT3 signaling and the inhibition of GBM tumorigenesis.
Glioblastoma (GBM) is the most prevalent type of adult primary brain tumor and chemotherapy of GBM was limited by drug-resistance. Fraxinellone is a tetrahydro-benzofuranone derivative with various pharmacological activities. However, the pharmacological effects of fraxinellone on GBM remains largely unknown. Here, we found that fraxinellone inhibited the proliferation and growth of GBM cells in a dose-dependent manner in vitro. Subsequently, we found that fraxinellone suppressed the migration and induced apoptosis of GBM cells in vitro. Using western blot and immunostaining, we further found that fraxinellone downregulated the expressions of sirtuin 3 (SIRT3), and superoxide dismutase 2 (SOD2), a downstream of SIRT3 in GBM cells. Meanwhile, reactive oxygen species (ROS) were increased in these fraxinellone-treated GBM cells. Interestingly, overexpression of SIRT3 (SIRT3-OE) indeed partially restored the inhibition of both cell proliferation and migration of GBM cells induced by fraxinellone. Finally, we found that fraxinellone could inhibit the growth of GBM in xenograft model through the inactivation of SIRT3 signaling pathway. Taken together, these results suggest that fraxinellone suppressed the growth and migration of GBM cells by downregulating SIRT3 signaling in vitro, and inhibited the tumorigenesis of GBMs in vivo.
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