Page 208 - 2025中醫藥與天然藥物聯合學術研討會-中醫藥與天然藥物的挑戰Ｘ機遇與未來大會手冊

PP-26

Isolation of furin inhibitors from Bishopwood (Bischofia javanica Blume)

and their effects on the metastasis of glioblastoma cells

#,1
Tran Mong To Tam, Pei-Wen Hsieh* ,1,2,3,4

1 Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan 33302, Taiwan
2 Graduate Institute of Natural Products, Chang Gung University, Taoyuan 33302, Taiwan
3 Department of General Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
4 Center for Drug Research and Development, Chang Gung University of Science and
Technology, Taoyuan 33303, Taiwan
* E-mail: pewehs@mail.cgu.edu.tw

Abstract
Furin, a key proprotein convertase, plays a critical role in mediating chemoresistance and
metastatic progression in glioblastoma (GBM). Despite its importance, therapeutic strategies
directly targeting furin remain largely unexplored, particularly those involving natural product–
derived inhibitors. In this study, a bioassay-guided fractionation approach was employed to
isolate and purify furin-inhibitory compounds from Bischofia javanica (BJ) water extracts using
chromatographic and spectroscopic techniques. The furin inhibitory activities of the purified
compounds were initially evaluated by enzymatic assays, followed by molecular docking to
assess binding affinity. Their therapeutic relevance was further examined in U-87MG
glioblastoma cells using CCK-8 proliferation assays, wound healing, and transwell migration
and invasion assays. Western blotting was subsequently performed to elucidate underlying
molecular mechanisms. Among them, gallic acid (GA) and two gallotannins (BJE50-5 and
BJE50-6) demonstrated significant furin inhibition, with IC₅₀ values of 66.71 ± 2.02, 39.09 ±
0.57, and 9.86 ± 0.37 µM, respectively. Molecular docking confirmed strong binding affinities
to furin. Notably, BJE50-5 and BJE50-6 more effectively suppressed furin activity in U-87MG
cells. While exhibiting no cytotoxic effects on proliferation, these compounds markedly
reduced cell migration and invasion in a concentration-dependent manner. Furthermore,
Western blot analyses revealed that BJE50-5 and BJE50-6 downregulated key proteins
associated with Notch and TGF-β/MMP signaling pathways. In conclusion, gallotannins
derived from Bischofia javanica exhibit potent furin-inhibitory activity and hold therapeutic
potential for GBM, particularly by suppressing metastatic progression.

Keywords: Bischofia javanica; Bishopwood; Gallotannin; Metastasis; Glioblastoma