Betulinic acid inhibits growth factor-induced in vitro angiogenesis via the modulation of mitochondrial function in endothelial cells

Ho Jeong Kwon, Joong Sup Shim, Jin Hee Kim, Hyun Young Cho, Young Na Yum, Seung Hee Kim, Jaehoon Yu

Research output: Contribution to journalArticle

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Abstract

Betulinic acid (BetA), a pentacyclic triterpene, is a selective apoptosis-inducing agent that works directly in mitochondria. Recent study has revealed that BetA inhibits in vitro enzymatic activity of aminopeptidase N (APN, EC 3.4.11.2), which is known to play an important role in angiogenesis, but the anti-angiogenic activity of BetA has not been reported yet. Data presented here show that BetA potently inhibited basic fibroblast growth factor (bFGF)-induced invasion and tube formation of bovine aortic endothelial cells (BAECs) at a concentration which had no effect on the cell viability. To access whether the anti-angiogenic nature of BetA originates from its inhibitory action against aminopeptidase N (APN) activity, the effect of BetA on APN was investigated. Surprisingly, BetA did not inhibit in vivo APN activity in endothelial cells or APN-positive tumor cells. On the other hand, BetA significantly decreased the mitochondrial reducing potential, and treatment with mitochondrial permeability transition (MPT) inhibitors attenuated BetA-induced inhibition of endothelial cell invasion. These results imply that anti-angiogenic activity of BetA occurs through a modulation of mitochondrial function rather than APN activity in endothelial cells.

Original languageEnglish
Pages (from-to)417-425
Number of pages9
JournalJapanese Journal of Cancer Research
Volume93
Issue number4
DOIs
Publication statusPublished - 2002 Jan 1

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CD13 Antigens
Intercellular Signaling Peptides and Proteins
Endothelial Cells
Pentacyclic Triterpenes
In Vitro Techniques
betulinic acid
Fibroblast Growth Factor 2
Permeability
Cell Survival
Mitochondria
Apoptosis

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kwon, Ho Jeong ; Shim, Joong Sup ; Kim, Jin Hee ; Cho, Hyun Young ; Yum, Young Na ; Kim, Seung Hee ; Yu, Jaehoon. / Betulinic acid inhibits growth factor-induced in vitro angiogenesis via the modulation of mitochondrial function in endothelial cells. In: Japanese Journal of Cancer Research. 2002 ; Vol. 93, No. 4. pp. 417-425.
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Betulinic acid inhibits growth factor-induced in vitro angiogenesis via the modulation of mitochondrial function in endothelial cells. / Kwon, Ho Jeong; Shim, Joong Sup; Kim, Jin Hee; Cho, Hyun Young; Yum, Young Na; Kim, Seung Hee; Yu, Jaehoon.

In: Japanese Journal of Cancer Research, Vol. 93, No. 4, 01.01.2002, p. 417-425.

Research output: Contribution to journalArticle

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AU - Shim, Joong Sup

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AU - Kim, Seung Hee

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