Effect of Ukrain on matrix metalloproteinase-2 and Secreted Protein Acidic and Rich in Cysteine (SPARC) expression in human glioblastoma cells.
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.
Gagliano
Nicoletta
N
Departments of Human Morphology-LITA Segrate, University of Milan, Milan, Italy. nicoletta.gagliano@unimi.it
Moscheni
Claudia
C
Torri
Carlo
C
Magnani
Ivana
I
Bertelli
Alberto A E
AA
Nowicky
Wassil
W
Gioia
Magda
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001600:Berberine Alkaloids / Q000494:pharmacology*; D015153:Blotting, Western; D001932:Brain Neoplasms; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology; D015676:Osteonectin / Q000378:metabolism*; D010617:Phenanthridines / Q000494:pharmacology*; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D001600:Berberine Alkaloids; D015676:Osteonectin; D010617:Phenanthridines; D012333:RNA, Messenger; C060921:ukrain; D020778:Matrix Metalloproteinase 2