TY - JOUR
T1 - N-ω-chloroacetyl-l-ornithine, a new competitive inhibitor of ornithine decarboxylase, induces selective growth inhibition and cytotoxicity on human cancer cells versus normal cells
AU - Medina-Enríquez, Miriam Marlene
AU - Alcántara-Farfán, Verónica
AU - Aguilar-Faisal, Leopoldo
AU - Trujillo-Ferrara, José Guadalupe
AU - Rodríguez-Páez, Lorena
AU - Vargas-Ramírez, Alba Laura
N1 - Publisher Copyright:
© 2014 Informa UK Ltd.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - Many cancer cells have high expression of ornithine decarboxylase (ODC) and there is a concerted effort to seek new inhibitors of this enzyme. The aim of the study was to initially characterize the inhibition properties, then to evaluate the cytotoxicity/antiproliferative cell based activity of N-chloroacetyl-l-ornithine (NCAO) on three human cancer cell lines. Results showed NCAO to be a reversible competitive ODC inhibitor (Ki=59μM) with cytotoxic and antiproliferative effects, which were concentration- and time-dependent. The EC50,72h of NCAO was 15.8, 17.5 and 10.1μM for HeLa, MCF-7 and HepG2 cells, respectively. NCAO at 500μM completely inhibited growth of all cancer cells at 48h treatment, with almost no effect on normal cells. Putrescine reversed NCAO effects on MCF-7 and HeLa cells, indicating that this antiproliferative activity is due to ODC inhibition.
AB - Many cancer cells have high expression of ornithine decarboxylase (ODC) and there is a concerted effort to seek new inhibitors of this enzyme. The aim of the study was to initially characterize the inhibition properties, then to evaluate the cytotoxicity/antiproliferative cell based activity of N-chloroacetyl-l-ornithine (NCAO) on three human cancer cell lines. Results showed NCAO to be a reversible competitive ODC inhibitor (Ki=59μM) with cytotoxic and antiproliferative effects, which were concentration- and time-dependent. The EC50,72h of NCAO was 15.8, 17.5 and 10.1μM for HeLa, MCF-7 and HepG2 cells, respectively. NCAO at 500μM completely inhibited growth of all cancer cells at 48h treatment, with almost no effect on normal cells. Putrescine reversed NCAO effects on MCF-7 and HeLa cells, indicating that this antiproliferative activity is due to ODC inhibition.
KW - Cancer
KW - Cell proliferation
KW - HeLa
KW - HepG2
KW - MCF-7
KW - ODC inhibitor
UR - http://www.scopus.com/inward/record.url?scp=84937036358&partnerID=8YFLogxK
U2 - 10.3109/14756366.2014.926342
DO - 10.3109/14756366.2014.926342
M3 - Artículo
C2 - 24939101
SN - 1475-6366
VL - 30
SP - 345
EP - 353
JO - Journal of Enzyme Inhibition and Medicinal Chemistry
JF - Journal of Enzyme Inhibition and Medicinal Chemistry
IS - 3
ER -