We investigated whether Ukrain modulates the malignant phenotype of clear cell 
renal cell carcinoma (ccRCC) cells Caki-1, Caki-2, and ACHN treated with four 
doses (5, 10, 20, and 40 μmol/l) for 24 and 48 h. The epithelial-to-mesenchymal 
transition markers E-cadherin, β-catenin, and vimentin were analyzed by 
immunofluorescence as well as actin and tubulin; matrix metalloproteinase-2 and 
matrix metalloproteinase-9 activity was analyzed by SDS-zymography, 
intracellular and secreted SPARC levels by western blot, and cell cycle by flow 
cytometry. Ukrain did not induce E-cadherin/β-catenin immunoreactivity at the 
cell-cell boundary, although it determined the actin cortical expression in 
Caki-2 and ACHN, and did not affect vimentin organization; however, in some 
Caki-1 and ACHN cells the perinuclear concentration of vimentin was consistent 
with its downregulation. Matrix metalloproteinase-2 and matrix 
metalloproteinase-9 activity was significantly downregulated 48 h after 20 
μmol/l Ukrain administration. At this time point, Ukrain significantly decreased 
migration and invasion, and downregulated SPARC levels in cell supernatants at 
all doses in Caki-2, and at 20 μmol/l in Caki-1 and ACHN cells. Concomitantly, 
SPARC was upregulated in all ccRCC cells, suggesting that Ukrain could also 
affect cell proliferation by cell cycle inhibition, as supported by the cell 
cycle analysis, as SPARC also acts as a cell cycle inhibitor. Our results 
suggest that Ukrain may switch the epithelial-to-mesenchymal transition-related 
phenotype of ccRCC cells, and targets the two major aspects involved in RCC 
progression, such as tumor invasion/microenvironment remodeling and cell 
proliferation.