Page 231 - 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-48

Stellettin B, a marine-sponge-derived compound, inhibits VEGF-induced

angiogenesis in human endothelial progenitor cells in vitro and in vivo

,2
1
Juei-Yu Yen, Jyh-Horng Sheu,* Shih-Wei Wang* ,1,3

1 Institute of Biomedical Science, MacKay Medical College, New Taipei City, Taiwan

2 Department of Marine Biotechnology and Resources, National Sun Yat-sen University,
Kaohsiung, Taiwan
3 Department of Medicine, MacKay Medical College, New Taipei City, Taiwan
* Email: shihwei@mmu.edu.tw

Abstract
Angiogenesis is a critical step in the physiology of tissue repair. Angiogenesis also plays an
important role during pathological processes, including various inflammatory diseases and
tumor progression. Accumulating evidence reports that bone marrow-derived endothelial
progenitor cells (EPCs) regulate angiogenesis. It has been suggested that understanding the
molecular targets and pharmacological functions of marine-derived natural products is
important for novel drug discovery. Stellettin B is a marine-sponge-derived triterpenoid and has
been found to exert anti-cancer, anti-invasion, and anti-angiogenic activity. However, the
function of stellettin B upon VEGF-induced angiogenesis on human endothelial progenitor cells
(EPCs) is undetermined. In this study, we found that stellettin B suppressed VEGF-induced
EPCs migration and tube formation in a concentration dependent manner. Furthermore, stellettin
B markedly abrogated VEGF-induced microvessel formation in both CAM-angiogenesis and
murine Matrigel implant models. Mechanistic investigations showed stellettin B inhibited
VEGF-induced phosphorylation of vascular endothelial growth factor receptor- 2 (VEGFR-2)
and its downstream signals, including Akt, Erk, p38 and Src in EPCs. This is the first
demonstration that stellettin B impeded VEGF-induced EPCs angiogenesis through VEGFR-2
dependent pathway on human EPCs. Stellettin B is a promising marine natural product worthy
of further development for the treatment of angiogenesis-related diseases.

Keywords: Angiogenesis; EPCs; Stellettin B