Presentation Title

Inhibition of Cancer Cell Viability Using Lysol Oxidase Inhibitors

Start Date

November 2016

End Date

November 2016

Location

HUB 379

Type of Presentation

Oral Talk

Abstract

Lysyl oxidase (LOX) is a copper-dependent amine oxidase that has been implicated in playing a paradoxical role in cancer. The enzyme’s main role is to catalyze the crosslinkages in collagen and elastin, and has also been implicated in the proliferation of tumors in late stage cancer. As a result, lysyl oxidase in breast cancer cells has been selected as a target for inhibition. It was hypothesized that the activity of LOX in cancer cells can be controlled through the use of the mechanism-based inhibitor 2-aminopropionitrile (β-APN). MDA-MB-231 breast cancer cells were used to test derivatized forms of this inhibitor. In particular, the meta and para derivatives of 4-nitrobenzyl β-APN, the para derivative of 4-bromobenzyl β-APN, the dibenzyl derivative of β-APN, and the 3,3-((4-bromobenzyl)azanediyl)dipropanenitrile were tested by means of viability assays. These assays revealed that cells treated with the meta derivative of 4-nitrobenzyl β-APN and the para derivative of 4-bromobenzyl β-APN had a significant decrease in cell viability when inhibitor concentrations greater than 500 μM were used. The para derivative of 4-nitrobenzyl β-APN, however, had little effect on the viability on the cells. These results indicate that the meta derivative of 4-nitrobenzyl β-APN and the para derivative of 4-bromobenzyl β-APN are successfully targeting the cancer cells.

In order to test whether the inhibitors were selectively targeting lysyl oxidase, western blot analysis using anti-LOX antibodies were carried out and fluorometric activity assays using Amplex red were performed. These assays showed that lysyl oxidase was present in cancer cells in large quantities and that the inhibitors had an effect on the activity. As a control, normal cells were also tested by western blot analysis and fluorometric activity assays were carried out. The controls showed that lysyl oxidase was present in normal cells as well, but to a lesser degree and almost 3.5 times less active than cancer cells. Given these data, it is proposed that lysyl oxidase is a good candidate for inhibition with these small-molecule -APN derivatives.

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Nov 12th, 10:15 AM Nov 12th, 10:30 AM

Inhibition of Cancer Cell Viability Using Lysol Oxidase Inhibitors

HUB 379

Lysyl oxidase (LOX) is a copper-dependent amine oxidase that has been implicated in playing a paradoxical role in cancer. The enzyme’s main role is to catalyze the crosslinkages in collagen and elastin, and has also been implicated in the proliferation of tumors in late stage cancer. As a result, lysyl oxidase in breast cancer cells has been selected as a target for inhibition. It was hypothesized that the activity of LOX in cancer cells can be controlled through the use of the mechanism-based inhibitor 2-aminopropionitrile (β-APN). MDA-MB-231 breast cancer cells were used to test derivatized forms of this inhibitor. In particular, the meta and para derivatives of 4-nitrobenzyl β-APN, the para derivative of 4-bromobenzyl β-APN, the dibenzyl derivative of β-APN, and the 3,3-((4-bromobenzyl)azanediyl)dipropanenitrile were tested by means of viability assays. These assays revealed that cells treated with the meta derivative of 4-nitrobenzyl β-APN and the para derivative of 4-bromobenzyl β-APN had a significant decrease in cell viability when inhibitor concentrations greater than 500 μM were used. The para derivative of 4-nitrobenzyl β-APN, however, had little effect on the viability on the cells. These results indicate that the meta derivative of 4-nitrobenzyl β-APN and the para derivative of 4-bromobenzyl β-APN are successfully targeting the cancer cells.

In order to test whether the inhibitors were selectively targeting lysyl oxidase, western blot analysis using anti-LOX antibodies were carried out and fluorometric activity assays using Amplex red were performed. These assays showed that lysyl oxidase was present in cancer cells in large quantities and that the inhibitors had an effect on the activity. As a control, normal cells were also tested by western blot analysis and fluorometric activity assays were carried out. The controls showed that lysyl oxidase was present in normal cells as well, but to a lesser degree and almost 3.5 times less active than cancer cells. Given these data, it is proposed that lysyl oxidase is a good candidate for inhibition with these small-molecule -APN derivatives.