Angelicin impedes the progression of glioblastoma via inactivation of YAP signaling pathway

Mengmeng Wang; Shuqiao Xing; Jiamei Jia; Weiquan Zeng; Jia Lei; Yiming Qian; Zhenrong Xiong; Xin Wang; Liying Cao; Yongjie Wang; Ying Wang; Yuanyuan Jiang; Zhihui Huang

doi:10.1016/j.biopha.2023.114462

Angelicin impedes the progression of glioblastoma via inactivation of YAP signaling pathway

Biomed Pharmacother. 2023 May:161:114462. doi: 10.1016/j.biopha.2023.114462. Epub 2023 Mar 16.

Authors

Affiliations

¹ School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
² Clinical Research Center, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 311121, China. Electronic address: nancywangying@163.com.
³ School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China. Electronic address: jiangyuanyuan@hznu.edu.cn.
⁴ School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China. Electronic address: huang0069@hznu.edu.cn.

PMID: 36933380
DOI: 10.1016/j.biopha.2023.114462

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.

Keywords: Angelicin; Cell cycle; GBM; Migration; Proliferation; YAP.

MeSH terms

Animals
Brain Neoplasms* / pathology
Cell Line, Tumor
Cell Proliferation
Furocoumarins* / pharmacology
Furocoumarins* / therapeutic use
Glioblastoma* / pathology
Humans
Mice
Mice, Inbred C57BL
Mice, Nude
Signal Transduction
Xenograft Model Antitumor Assays

Substances

Furocoumarins