Investigation of the composition and antibacterial activity of Ukrain™ drug using liquid chromatography techniques.

The greater celandine (Chelidonium majus L.) has been known for the centuries as a medicinal plant. One of the therapeutic agents based on C. majus is anticancer drug Ukrain™ known as a semi-synthetic C. majus alkaloid derivative. Although there are no doubts about antitumor properties of the drug, there is still controversy about its composition. In this study, Ukrain™ was subjected to TLC and LC-MS/MS analyses to compare it with C. majus alkaloid root extract and to determine its composition. Moreover, microbiological activity of both Ukrain™ and the alkaloid extract were tested against Bacillus subtilis strains using TLC-direct bioautography. Sanguinarine, chelidonine, α-homochelidonie and chelerythrine were found to have antibacterial properties. Besides chelidonine, sanguinarine, chelerythrine, protopine, allocryptopine, homochelidonie, berberine and coptisine reported earlier in literature, the presence of stylopine, norchelidonine, dihydrochelidonine and hydroberberine in Ukrain™ was detected, and here they have been reported for the first time.

Ukrain modulates glial fibrillary acidic protein, but not connexin 43 expression, and induces apoptosis in human cultured glioblastoma cells.

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.

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.

Efficacy of ukrain in the treatment of pancreatic cancer.

BACKGROUND: This monocentric study evaluated the effect of ukrain in the treatment of pancreatic cancer. MATERIAL AND METHODS: Between January 1996 and December 1999 we treated 21 patients with 10 mg ukrain every second day x10. The control group received supportive treatment only. RESULTS: Ukrain treatment was well tolerated. Mean values on pain measure and Karnofsky index were significantly better in the ukrain group than in controls ( P<0.05). One-year survival was 76% in the ukrain group, compared to 9.5% in the control group. Median survival after treatment with ukrain was 574 days, compared to 197 days in the control group. CONCLUSIONS: Our data demonstrate that ukrain improves quality of life in patients suffering from advanced pancreatic cancer and significantly prolongs survival time in these patients.