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 126.96.36.199), 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.
|Number of pages||9|
|Journal||Japanese Journal of Cancer Research|
|Publication status||Published - 2002 Jan 1|
All Science Journal Classification (ASJC) codes
- Cancer Research