Abstract
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.
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Acknowledgements
We are grateful to Professor Kang-sheng Li, Yi Guan, Dr. Chun-yan Li, Dr. Tian Li and Mr. Ge-jun Li for their technical assistance and experimental material support. This work was supported by the Research Foundation of Hunan Administration of Traditional Chinese Medicine (No. 2019101); Natural Science Foundation of Hunan province (No. 2019JJ50631); Research Foundation of Guangdong Administration of Traditional Chinese Medicine (No. 20202090).
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JW, RL, XYJ designed the research and wrote the article; CQX, JXS, DLC, MJL directed the experiment and data analysis; CQX, RL, RNH, ZHL performed the vitro experiments and analyzed the data; RL, QYR, CHL, RTZ did the in vivo experiments and analyzed the data.
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All experimental procedures in the current study were approved by Shan tou University Animal Care Committee (approval number: SUMC2019-173).
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Li, R., Xu, Cq., Shen, Jx. et al. 4-Methoxydalbergione is a potent inhibitor of human astroglioma U87 cells in vitro and in vivo. Acta Pharmacol Sin 42, 1507–1515 (2021). https://doi.org/10.1038/s41401-020-00560-w
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DOI: https://doi.org/10.1038/s41401-020-00560-w
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