4-Methoxydalbergione is a potent inhibitor of human astroglioma U87 cells in vitro and in vivo

Ran Li1, Chang-qiong Xu1, Jian-xin Shen1, Qiu-yun Ren1, Di-ling Chen2, Mian-jie Lin1, Rong-ni Huang1, Chun-hui Li, Ru-ting Zhong1, Zhi-hua Luo1, Xiao-yu Ji1, Jie Wu1
1 Brain Function and Disease Laboratory, Shantou University Medical College, Shantou 515041, China
2 Guangdong Institute of Microbiology, Guangzhou 510070, China and 3Yueyang Hospital of Traditional Chinese Medicine, Yueyang 414000, China
Correspondence to: Xiao-yu Ji:, Jie Wu:,
DOI: 10.1038/s41401-020-00560-w
Received: 15 May 2020
Accepted: 19 October 2020
Advance online: 11 December 2020


Astroglioma is the most common primary tumor in the central nervous system without effective treatment strategies. Temozolomide (TMZ) is a chemotherapeutic drug to treat astroglioma but exhibits low potency and has side effects. Therefore, there is an urgent need to develop new compounds to treat astroglioma. Dalbergia sissoo Roxb was the source of Dalbergia odorifera in traditional Chinese medicine (TCM) and has been clinically used as an anti-tumor medicine. 4‐Methoxydalbergione (4MOD) is purified from Dalbergia sissoo Roxb., and shows an inhibitory effect on osteosarcoma, but its effects on astroglioma have not been reported. Here, we evaluate its anti-astroglioma effects on both in vitro and in vivo models. In cultured astroglioma U87 cells, 4MOD inhibited cell proliferation and induced cell apoptosis in a time- and concentration-dependent manner. Compared with TMZ, 4MOD exhibited a tenfold greater potency of anti-astroglioma effects. 4MOD effectively stalled the cell cycle in G2 phase. Transcriptome sequencing (RNA-seq) showed that 4MOD upregulated 158 genes and downregulated 204 genes that are mainly enriched in cell membrane, cell division, cell cycle, p53, TNF, and MAPK signaling pathways, which may underlie its anti-tumor mechanisms. In a nude mouse xenograft model transplanted with U87 cells, 10 mg/kg 4MOD slowed down tumor growth rate, while at 30 mg/kg dose, it reduced tumor size. Collectively, this study demonstrates that 4MOD is a potent native compound that remarkably inhibits U87 astroglioma growth in both in vitro and in vivo models.
Keywords: Dalbergia sissoo Roxb; 4‐methoxydalbergione; human astroglioma U87 cell line; RNA-seq; cell cycle; apoptosis

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