期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 890, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2020.173669
关键词
Eucalyptal a; Glioma; Oncogenic splicing; Serine/arginine-rich splicing factor 1; Myosin 1B
资金
- China Scholarship Council [201606945004]
- National Natural Science Foundation of China [81402050, 81502166, 81672592, 81872061, 81972354]
- Programs of Science and Technology Bureau Foundation of Tianjin Municipality [16JCQNJC13400, 17JCYBJC27100, 19JCZDJC64900 (Z)]
- Program of Tianjin Municipal Health Bureau [15KG147]
- New Century Talent Training Project of TMUGH
- Tianjin Higher Education Science and Technology Development Project [2019ZD031]
Eucalyptal A is identified as an important lead compound with anti-glioblastoma activity, inhibiting cell proliferation and invasiveness to prolong overall survival time, and exerting anti-tumor effects through modulation of relevant pathways.
Glioma is the most common primary intracranial tumor, in which glioblastoma (GBM) is the most malignant and lethal. However, the current chemotherapy drugs are still unsatisfactory for GBM therapy. As the natural products mainly extracted from Eucalyptus species, phloroglucinol-terpene adducts have the potential to be anticancer lead compounds that attracted increasing attention. In order to discover the new lead compounds with the anti-GBM ability, we isolated Eucalyptal A with a phloroglucinol-terpene skeleton from the fruit of E. globulus and investigated its anti-GBM activity in vitro and in vivo. Functionally, we verified that Eucalyptal A could inhibit the proliferation, growth and invasiveness of GBM cells in vitro. Moreover, Eucalyptal A had the same anti-GBM activity in tumor-bearing mice as in vitro and prolonged the overall survival time by maintaining mice body weight. Further mechanism research revealed that Eucalyptal A downregulated SRSF1 expression and rectified SRSF1-guided abnormal alternative splicing of MYO1B mRNA, which led to anti-GBM activity through the PDK1/AKT/c-Myc and PAK/Cofilin axes. Taken together, we identified Eucalyptal A as an important antiGBM lead compound, which represents a novel direction for glioma therapy.
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