Kathryn A Johnston
California State University, USA
Title: Inhibition of Lysyl oxidase in breast cancer cells by small-molecule inhibitors
Biography
Biography: Kathryn A Johnston
Abstract
Lysyl oxidase (LOX) is an extracellular matrix, copper-dependent, amine oxidase that catalyzes a key crosslinking step in
collagen and elastin. Th is enzyme has also been shown to play a role in promoting metastasis. Th e correlation between
high LOX activity and cancer metastasis is strong enough that upregulated LOX activity can be used as a diagnostic marker for
the severity of cancer in patients. β-aminopropionitrile is a known potent inhibitor of lysyl oxidase; however, this inhibitor is
not selective and, therefore, cannot be used as a therapeutic agent. β-aminopropionitrile has been derivatized using aromatic
sidechains and has been used to selectively target lysyl oxidase in breast cancer cells. Th e inhibitor LP-1-2 has been shown to
reduce breast cancer cell viability with a 100 μM dose and 72-hour incubation period. Th e eff ect on cell viability increased
with increasing amounts of inhibitor. Th e selective targeting of lysyl oxidase was verifi ed using western blot analysis and lysyl
oxidase activity assays. Th e activity assays showed that addition of increasing amounts of inhibitor decreased the activity of
lysyl oxidase. Th e highest level of inhibition detected was with lysyl oxidase isolated from cells treated with 5000 μM of LP-1-2
for 3 days, which decreased the activity three-fold as compared to lysyl oxidase isolated from untreated cells.