Glioblastoma is a highly malignant
tumor, characterized by an unfavorable prognosis even in response to multidisciplinary treatment strategies, owing to its high-invasive phenotype.
Ukrain, a semisynthetic
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. In particular, we previously demonstrated that
Ukrain modulates the expression of genes and
proteins involved in
tumor invasion, and here we investigate some unreported effects of
Ukrain on human cultured
glioblastoma cells. We used morphological and molecular biology methods to analyze the expression and the intracellular distribution pattern of
glial fibrillary acidic protein, the expression of the
gap junction protein connexin 43 and the apoptotic effect in human
glioblastoma cells treated with 0.1, 1 and 10 micromol/l
Ukrain for 72 h.
After treatment with 10 micromol/l
Ukrain,
glial fibrillary acidic protein fluorescence increased and a higher number of cells displayed
glial fibrillary acidic protein organized into a filamentous state. Western blot analysis of
glial fibrillary acidic protein confirmed that
Ukrain tended to upregulate the
protein.
Connexin 43 was not modulated by
Ukrain both at the
mRNA and at the
protein level.
Ukrain-induced apoptotic rate was 4.63, 10.9 and 28.9% after 0.1, 1 and 10 micromol/l
Ukrain, respectively, likely mediated by
cytochrome c release in the cytoplasm. Considered as a whole, these findings provide new information to complete the understanding of the mechanisms of
Ukrain antitumor and chemopreventive effect, and support the possible potential of
Ukrain for the
therapy of
brain tumors.