Anti-cancer activity of an osthole derivative, NBM-T-BMX-OS01: Targeting vascular endothelial growth factor receptor signaling and angiogenesis

Hung Yu Yang, Ya Fen Hsu, Pei Ting Chiu, Shiau Jing Ho, Chi Han Wang, H. N. Chi, Yu Han Huang, Cheng Feng Lee, Ying Shiuan Li, George Ou, Ming Jen Hsu

Research output: Contribution to journalArticle

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Abstract

Angiogenesis occurs during tissue growth, development and wound healing. It is also required for tumor progression and represents a rational target for therapeutic intervention. NBM-T-BMX-OS01 (BMX), derived from the semisynthesis of osthole, an active ingredient isolated from Chinese herb Cnidium monnieri (L.) Cuss., was recently shown to enhance learning and memory in rats. In this study, we characterized the anti-angiogenic activities of NBM-T-BMX-OS01 (BMX) in an effort to develop novel inhibitors to suppress angiogenesis and tumor growth. BMX inhibited vascular endothelial growth factor (VEGF)-induced proliferation, migration and endothelial tube formation in human umbilical endothelial cells (HUVECs). BMX also attenuated VEGF-induced microvessel sprouting from aortic rings ex vivo and reduced HCT116 colorectal cancer cells-induced angiogenesis in vivo. Moreover, BMX inhibited the phosphorylation of VEGFR2, FAK, Akt and ERK in HUVECs exposed to VEGF. BMX was also shown to inhibit HCT116 cell proliferation and to suppress the growth of subcutaneous xenografts of HCT116 cells in vivo. Taken together, this study provides evidence that BMX modulates vascular endothelial cell remodeling and leads to the inhibition of tumor angiogenesis. These results also support the role of BMX as a potential drug candidate and warrant the clinical development in the treatment of cancer.

Original languageEnglish
Article numbere81592
JournalPLoS One
Volume8
Issue number11
DOIs
Publication statusPublished - Nov 27 2013

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vascular endothelial growth factor receptors
Vascular Endothelial Growth Factor Receptor
angiogenesis
Vascular Endothelial Growth Factor A
vascular endothelial growth factors
Tumors
chemical derivatives
Endothelial cells
HCT116 Cells
Derivatives
neoplasms
endothelial cells
Cnidium
Neoplasms
Phosphorylation
Endothelial Cells
Cell proliferation
umbilicus
Umbilicus
Heterografts

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Anti-cancer activity of an osthole derivative, NBM-T-BMX-OS01 : Targeting vascular endothelial growth factor receptor signaling and angiogenesis. / Yang, Hung Yu; Hsu, Ya Fen; Chiu, Pei Ting; Ho, Shiau Jing; Wang, Chi Han; Chi, H. N.; Huang, Yu Han; Lee, Cheng Feng; Li, Ying Shiuan; Ou, George; Hsu, Ming Jen.

In: PLoS One, Vol. 8, No. 11, e81592, 27.11.2013.

Research output: Contribution to journalArticle

Yang, Hung Yu ; Hsu, Ya Fen ; Chiu, Pei Ting ; Ho, Shiau Jing ; Wang, Chi Han ; Chi, H. N. ; Huang, Yu Han ; Lee, Cheng Feng ; Li, Ying Shiuan ; Ou, George ; Hsu, Ming Jen. / Anti-cancer activity of an osthole derivative, NBM-T-BMX-OS01 : Targeting vascular endothelial growth factor receptor signaling and angiogenesis. In: PLoS One. 2013 ; Vol. 8, No. 11.
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