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.com
Volume 8
Journal of Biotechnology & Biomaterials
ISSN: 2155-952X
Biotech Congress 2018 & Enzymology 2018
March 05-07, 2018
JOINT EVENT
20
th
Global Congress on
Biotechnology
3
rd
International Conference on
Enzymology and Molecular Biology
&
March 05-07, 2018 London, UK
Inhibition of Lysyl oxidase in breast cancer cells by small-molecule inhibitors
Kathryn A Johnston
and
Karlo M Lopez
California State University, USA
L
ysyl oxidase (LOX) is an extracellular matrix, copper-dependent, amine oxidase that catalyzes a key crosslinking step in
collagen and elastin. This enzyme has also been shown to play a role in promoting metastasis. The 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. The inhibitor LP-1-2 has been shown to
reduce breast cancer cell viability with a 100 μM dose and 72-hour incubation period. The effect on cell viability increased
with increasing amounts of inhibitor. The selective targeting of lysyl oxidase was verified using western blot analysis and lysyl
oxidase activity assays. The activity assays showed that addition of increasing amounts of inhibitor decreased the activity of
lysyl oxidase. The 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.
Recent Publications
1. Johnston, K. and Lopez, K. (2017) Minireview: Lysyl Oxidase in Cancer Inhibition and Metastasis, Cancer Letters,
417, 174 – 181.
2. Oldfield R, Johnston K, Limones J, Ghilarducci C and Lopez K (2017) Identification of histidine 303 as the catalytic
base of lysyl oxidase via site - directed mutagenesis. The Protein Journal. Doi: 10.1007/s10930-017-9749-3.
3. Smith M A, Gonzalez J, Hussain A, Oldfield R N et al. (2016) Overexpression of soluble recombinant human lysyl
oxidase by using solubility tags: effects on activity and solubility. Enzyme Research. 2016. Doi: 10.1155/2016/5098985.
Biography
Kathryn A Johnston is a fourth–year Senior Student at California State University, Bakersfield and has worked in Dr. Lopez’s laboratory for the past two and a
half years. During this period, she has published three papers. Her work deals primarily with the inhibition and reduction of viability of breast cancer cells using
derivatized inhibitors of β-aminopropionitrile. She has presented her work as posters and invited talks at regional meetings, as well as national meetings of the
American Chemical Society.
kjohnston3@csub.eduKathryn A Johnston et al., J Biotechnol Biomater 2018, Volume 8
DOI: 10.4172/2155-952X-C2-092