Objective

Renal cell carcinoma (RCC) is a common type of cancer worldwide. In 2014, there were over 12,000 new cases in the UK alone, with more occurring in males than females. Different histological subtypes are found in RCC, the commonest (>80%) being clear cell RCC (ccRCC), which originates in the proximal convoluted tubes. Mutations in the von Hippel–Lindau (VHL) gene occur in more than 90% of all sporadic cases of ccRCC.

The lysyl oxidase (LOX) family consists of LOX and four LOX-like enzymes (LOXL1-LOXL4) which are involve in extracellular matrix remodelling. Collagen crosslinking in the extracellular matrix catalysed by LOX and LOXL2, can promote tumour progression and metastasis in the kidney.

In this study, ccRCC cell line Caki-2 cells were treated with potential LOX and LOXL2 inhibitors consisting of three novel synthesized compounds (designated 1, 4, 5) at concentrations of 10, 50 and 200 ug/ml for 24, 48 or 72 hours. The activity of LOX were measured following treatment. The expressions of LOX and LOXL2 were evaluated using qRT-PCR. The effects of these compounds on Caki-2 cell proliferation, migration, viability and on their production of NAD(P)H were determined as well.

It was found that all three compounds inhibited LOX activity, with compound 4 showing greater inhibitory effects than the other two. Both LOX and LOXL2 mRNA expressions were downregulated by these compounds.  Compound 4 decreased Caki-2