Anticancer Drugs. 2006 Feb;17(2):189-94.
Effect of Ukrain on matrix metalloproteinase-2 and Secreted Protein Acidic and
Rich in Cysteine (SPARC) expression in human glioblastoma cells.
Gagliano N, Moscheni C, Torri C, Magnani I, Bertelli AA, Nowicky W, Gioia M.
Departments of Human Morphology-LITA Segrate, University of Milan, Milan, Italy.
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Glioblastoma is a highly malignant brain tumor with a highly invasive phenotype
and hence an unfavorable prognosis even in response to multidisciplinary
treatment strategies. Ukrain, a semi-synthetic thiophosphoric acid derivative of
the purified alkaloid chelidonine, has been used in the therapy of several solid
tumors, but little is known about its effect on glioblastoma and, in general,
about the molecular mechanisms responsible for its effects. We used RT-PCR,
Western blot and SDS-zymography to investigate the effects of three doses of
Ukrain (0.1, 1 and 10 micromol/l) on the expression of genes and proteins
involved in the extracellular matrix remodeling associated with tumor invasion in
human cultured glioblastoma cells treated for 24, 48 and 72 h. We analyzed the
expression of matrix metalloproteinase-2 and -9, the main mediators of
glioblastoma invasiveness, and secreted protein acidic and rich in cysteine
(SPARC), involved in the regulation of cell-matrix interactions. There was a
significant, dose-related decrease of glioblastoma cell proliferation and a
tendency to downregulation of SPARC at the protein level 72 h after 10 micromol/l
Ukrain, suggesting the drug may be a useful therapeutic tool for brain tumors.