Angelicin impedes the progression of glioblastoma via inactivation of YAP signaling pathway - 28/03/23

Doi : 10.1016/j.biopha.2023.114462

Mengmeng Wang ^a,^b,^c,^d,^{^{1
These authors have contributed equally to this work and share first authorship}}, Shuqiao Xing ^a,^b,^c,^d,^{^{1
These authors have contributed equally to this work and share first authorship}}, Jiamei Jia ^a,^b,^c,^d, Weiquan Zeng ^a,^b,^c,^d, Jia Lei ^a,^b,^c,^d, Yiming Qian ^a,^b,^c,^d, Zhenrong Xiong ^a,^b,^c,^d, Xin Wang ^a,^b,^c,^d, Liying Cao ^a,^b,^c,^d, Yongjie Wang ^a,^b,^c,^d, Ying Wang ^e,^⁎ , Yuanyuan Jiang ^a,^b,^c,^d,^⁎ , Zhihui Huang ^a,^b,^c,^d,^⁎
^a School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
^b Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
^c Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Zhejiang 311121, China
^d Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
^e Clinical Research Center, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 311121, China

^⁎Corresponding authors at: School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.School of Pharmacy, Hangzhou Normal UniversityHangzhouZhejiang311121China^⁎⁎Corresponding author.

Abstract

Glioblastoma (GBM) is a human malignant tumor with low survival and high recurrence rate. Angelicin, an active furanocoumarin compound, has been reported to possess potential antitumor activity towards various malignancies. However, the effect of angelicin on GBM cells and its mechanism are still unclear. In this study, we found that angelicin inhibited the proliferation of GBM by inducing the cell cycle arrested in G1 phase and suppressed the migration of GBM cells in vitro. Mechanically, we found that angelicin downregulated the expression of YAP and decreased the nuclear localization of YAP, and suppressed the expression of β-catenin. Furthermore, overexpression of YAP partially restored the inhibitory effect of angelicin on GBM cells in vitro. Finally, we found that angelicin could inhibit the growth of tumor and reduce the expression of YAP in the subcutaneous xenograft model of GBM in nude mice and the syngeneic intracranial orthotopic model of GBM in C57BL/6 mice. Taken together, our results suggest that the natural product angelicin exerts its anticancer effects on GBM via YAP signaling pathway, and is expected to be a promising compound for the treatment of GBM.

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Highlights

•	Angelicin inhibits the proliferation and migration of GBM cells in vitro.
•	Angelicin decreases the expression and nucleus translocation of YAP in vitro.
•	YAP overexpression partly abolishes the inhibitory effect of angelicin in vitro.
•	Angelicin inhibits the growth of GBM and reduces the YAP expression in vivo.

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Abbreviations : Ang, GBM, YAP

Keywords : Angelicin, GBM, YAP, Proliferation, Cell cycle, Migration

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Vol 161

Article 114462- mai 2023 Retour au numéro

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Angelicin impedes the progression of glioblastoma via inactivation of YAP signaling pathway - 28/03/23

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