DEGUCHI Atsuko    Department   Graduate School of Medical Science, Graduate School of Medical Science    Position   Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Induction of G1 arrest and selective growth inhibition by lactacystin in human umbilical vein endothelial cells.
Journal	Formal name：Anticancer Research ISSN code：17917530
Domestic / Foregin	Foregin
Volume, Issue, Page	19(5B),pp.3961-3968
Author and coauthor	Kumeda S, Deguchi A, Toi M, Omura S, and Umezawa K.
Authorship	2nd author
Publication date	1999
Summary	In search for angiogenesis inhibitors, we tested protease and proteasome inhibitors for the induction of G1 arrest and selective inhibition of growth of human umbilical vein endothelial cells (HUVECs). Serine protease-, cysteine protease-, aspartate protease-, and aminopeptidase-inhibitors did not inhibit bFGF/FBS-induced S-phase induction in HUVECs, but a proteasome inhibitor, lactacystin did inhibit it reversibly. Lactacystin increased the cellular level of p53 and cdk2-associated p21WAF1/CIP1 leading to cdk2 inactivation. In addition to the angiogenesis inhibitor TNP-470, lactacystin also inhibited the growth of HUVECs selectively at about a 20 times lower concentration than that of other human cell lines, including normal fibroblasts and carcinoma cells. Lactacystin induced p53-dependent p21WAF1/CIP1 expression at lower concentrations in HUVECs than in other cells. These cellular effects were also observed with a tripeptide-type proteasome inhibitor, N-Ac-Leu-Leu-norleucinal.