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Old 03-30-2010, 12:28 PM   #1
Rich66
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Ukrain/Celandine

ACS summary
Quote:
Available scientific evidence does not support claims about the benefits of celandine.
Quote:
Researchers recently found that celandine may be responsible for many unexplained cases of hepatitis.
MSKCC entry
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A recent systematic review of clinical trials suggests that Ukrain may have potential as an anticancer drug but well designed studies are needed (7
cam-cancer.org discussion (includes cost)
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It is not FDA-approved in the US but is approved in Mexico, and the United Arab Emirates as a standard anticancer medication.
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Ukrain has also been designated as an Orphan Drug for pancreatic cancer in the USA and in Australia.28
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The costs of Ukrain therapy are high; one course costs €700 for the medication alone, and the total treatment costs have been estimated to be around €3,000 per week.22
For ten injections of 10-20 mg intravenously the total cost of medication itself is approximately $3,500.00 (€2,891). This includes shipping, handling, bank transfer and prescription.
Nowicky Pharma (source, studies, case reports)

http://www.ralphmoss.com/ukrain.html
Quote:
A study of 70 "terminal" cancer patients, conducted under contract to the Ministry of Science and Research of Austria, found that the drug was: "Cytostatic or cytotoxic to human leukemias, non small and small cell lung cancers, colon cancers, central nervous system cancer, melanomas, ovarian cancer and renal cancer."
Interestingly, in the NCI cell studies, the drug was found to yield special inhibition of colon, stomach, ovarian, kidney, small cell and non small cell and melanoma cells—almost identical to what was seen clinically.
http://www.proukrain.com/
Quote:
UKRAIN:
  • is toxic against cancer cells at the therapeutic dose but not against healthy cells
  • accumulates at the site of the tumour very rapidly after injection
  • brings about the encapsulation of larger tumours through anti-angiogenesis (the inhibition of new blood vessels at the tumour site), thereby increasing operability
  • regenerates the immune system
363 cancer patients with 47 different types of tumour were treated with UKRAIN between September 1997 and January 2003 at the Villa Medica Clinic (Edenkoben, Germany) under the medical direction of Dr. Aschhoff. These patients had already exhausted conventional means of therapy without success, and because of relapse and/or continued progression of the disease, UKRAIN therapy was undertaken. The following rates of full remission were achieved: breast cancer 31%, colorectal cancer 16.7%, bronchial adenocarcinoma 7.7%, small-cell bronchial carcimoma 21%, astrozytoma (brain tumor) 66.6%, neuroblastoma 60%, seminoma (testicular cancer) 75%, bladder carcinoma 50% (181, 189).
Ukrain – a new cancer cure? A systematic review of randomised clinical trials


FULL TEXT



E Ernst and K Schmidt
Complementary Medicine, Peninsula Medical School, Universities of Exeter & Plymouth, 25 Victoria Park Road, Exeter EX2 4NT

author email corresponding author email
BMC Cancer 2005, 5:69doi:10.1186/1471-2407-5-69
The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2407/5/69
Received: 17 March 2005
Accepted: 1 July 2005
Published: 1 July 2005
© 2005 Ernst and Schmidt; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract

Background

Ukrain is an anticancer drug based on the extract of the plant Chelidonium majus L. Numerous pre-clinical and clinical investigations seem to suggest that Ukrain is pharmacologically active and clinically effective. We wanted therefore to critically evaluate the clinical trial data in the form of a systematic review.
Methods

Seven electronic databases were searched for all relevant randomised clinical trials. Data were extracted and validated by both authors, tabulated and summarised narratively. The methodological quality was assessed with the Jadad score.
Results

Seven trials met our inclusion criteria. Without exception, their findings suggest that Ukrain has curative effects on a range of cancers. However, the methodological quality of most studies was poor. In addition, the interpretation of several trials was impeded by other problems.
Conclusion

The data from randomised clinical trials suggest Ukrain to have potential as an anticancer drug. However, numerous caveats prevent a positive conclusion, and independent rigorous studies are urgently needed.



Drugs Exp Clin Res. 2000;26(5-6):341-56.
Ukrain: a novel antitumor drug.


Uglyanitsa KN, Nefyodov LI, Doroshenko YM, Nowicky JW, Volchek IV, Brzosko WJ, Hodysh YJ.
Medical Institute of Grodno, ul Gorkogo 80, 230015 Grodno, Belarus.
A review of the recent literature on the new anticancer drug Ukrain is provided herein. We review Ukrain, a thiophosphate derivative of alkaloids from Chelidonium majus L., its capacity to exert selective cytotoxic and cytostatic effects on tumor cells, simultaneously acting as an immune response modifier, its good tolerance and lack of side effects even after long-term application, perspectives of the application of this drug in oncology.

PMID: 11345050 [PubMed - indexed for MEDLINE]





Hepatogastroenterology. 2007 Apr-May;54(75):917-20.
The clinical efficacy of adjuvant systemic chemotherapy with gemcitabine and NSC-631570 in advanced pancreatic cancer.

Gansauge F, Ramadani M, Schwarz M, Beger HG, Lotspeich E, Poch B.
Center for Oncological, Endocrinological and Minimal-access Surgery, University of Ulm, Silcherstr. 36, 89231 Neu-Ulm, Germany. frank.gansauge@eurosurgery.de
BACKGROUND/AIMS: Recently we have shown that NSC-631570 (Ukrain) is a safe and effective drug in the treatment of unresectable pancreatic cancer. The aim of this study was to determine the effectiveness of the combined treatment with Gemcitabine and NSC-631570 in the adjuvant treatment of resected advanced pancreatic cancer. METHODOLOGY: 30 patients received adjuvant chemotherapy following surgical resection for pancreatic cancer. Chemotherapy consisted of Gemcitabine according to the Burris-protocol with weekly infusions of 1000 mg/sqm. Immediately following Gemcitabine infusion 20mg of NSC-631570 were administered intravenously over 15 minutes. RESULTS: WHO grade II toxicities were observed in 53%, no WHO grade III or IV toxicities occurred. In 80% of the patients recurrence of the disease was observed. The relapse-free survival time was 21.7 months. The actuarial survival rates were 86.7% after one year, 76.6% after two years, 46.7% after three years and 23.3% after five years. The median survival time according to Kaplan-Meier regression analysis was 33.8 months. CONCLUSIONS: Adjuvant chemotherapy in advanced stages of pancreatic cancer using the combination of Gemcitabine and NSC-631570 is a safe treatment and seems to lead to a prolonged survival. Although further investigation is needed to confirm these results, the combined treatment of Gemcitabine and NSC-631570 is a promising therapy for the adjuvant treatment of resectable advanced pancreatic cancer.

PMID: 17591092 [PubMed - indexed for MEDLINE]




Langenbecks Arch Surg. 2002 Jun;387(2):84-9. Epub 2002 Jun 19.
Efficacy of ukrain in the treatment of pancreatic cancer.

Zemskov V, Prokopchuk O, Susak Y, Zemskov S, Tkachenko O, Hodysh Y, Nowicky W.
Department of General Surgery, National Medical University, prosp. Holosiivsky, 59B, 03039 Kyiv, Ukraine.
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.

PMID: 12111260 [PubMed - indexed for MEDLINE]






Langenbecks Arch Surg. 2002 Mar;386(8):570-4. Epub 2002 Feb 13.
NSC-631570 (Ukrain) in the palliative treatment of pancreatic cancer. Results of a phase II trial.

Gansauge F, Ramadani M, Pressmar J, Gansauge S, Muehling B, Stecker K, Cammerer G, Leder G, Beger HG.
Department of General Surgery, University of Ulm, Germany.
BACKGROUND: NSC-631570 (Ukrain) is a semisynthetic compound of thiophosphoric acid and the alkaloid chelidonine from the plant Chelidonium majus. It has been used in complementary herbal medicine for more than 20 years for the treatment of benign and malignant tumors. PATIENTS/METHODS: Between August 1999 and June 2001, 90 patients with histologically proven unresectable pancreatic cancer were randomized in a monocentric, controlled, randomized study. Patients in arm A received 1000 mg gemcitabine/m2, those in arm B received 20 mg NSC-631570, and those in arm C received 1000 mg gemcitabine/m2 followed by 20 mg NSC-631570 weekly. End point of the study was overall survival. RESULTS: In all three arms therapy was well tolerated and toxicity was moderate. At the first re-evaluation in arm A 32%, in arm B 75%, and in arm C 82% showed no change or partial remission according to WHO criteria (arm A versus arm B: P<0.01, arm A versus arm C: P<0.001). Median survival according to Kaplan-Meier analysis was in arm A 5.2 months, in arm B 7.9 months, and in arm C 10.4 months (arm A versus arm B: P<0.01, arm A versus arm C: P<0.01). Actuarial survival rates after 6 months were 26%, 65% and 74% in arms A B and C, respectively (arm A versus arm B: P<0.05, arm A versus arm C P<0.01). CONCLUSION: We could show that in unresectable advanced pancreatic cancer, NSC-631570 alone and in combination with gemcitabine nearly doubled the median survival times in patients suffering from advanced pancreatic cancer.

PMID: 11914932 [PubMed - indexed for MEDLINE]




Anticancer Drugs. 2007 Jul;18(6):669-76.
Ukrain modulates glial fibrillary acidic protein, but not connexin 43 expression, and induces apoptosis in human cultured glioblastoma cells.

Gagliano N, Moscheni C, Torri C, Donetti E, Magnani I, Costa F, Nowicky W, Gioia M.
Department of Human Morphology, San Paolo School of Medicine, University of Milan, Italy. nicoletta.gagliano@uimi.it
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.

PMID: 17762395 [PubMed - indexed for MEDLINE]




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. nicoletta.gagliano@unimi.it
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.

PMID: 16428937 [PubMed - indexed for MEDLINE]





Anticancer Drugs. 2006 Oct;17(9):1025-30.
In-vitro toxicity of Ukrain against human Ewing tumor cell lines.

Lanvers-Kaminsky C, Nolting DM, Köster J, Schröder A, Sandkötter J, Boos J.
Department of Pediatric Hematology and Oncology, University Children's Hospital, Münster, Germany.
Comment in:
Ukrain is advertised by the manufacturer as a drug for alternative cancer cures with high activity against progressive Ewing tumors. Using the MTT assay, we compared the cytotoxicity of Ukrain with the cytotoxicity of N,N',N''-triethylenethiophosphoramide (thioTEPA), Chelidonium majus L. alkaloids, doxorubicin, cyclophosphamide and etoposide against four human Ewing tumor cell lines. In addition, we studied the cytotoxicity of thioTEPA combined with C. majus L. alkaloids after 48, 72 and 96 h. All compounds reduced the growth of Ewing tumor cell lines in a dose-dependent manner. The concentrations that reduced cell growth by 50% ranged between 6.2 and 31.1 micromol/l for Ukrain, 1.9 and 26.1 micromol/l for C. majus L. extract, and 1.7 and 448 micromol/l for thioTEPA. The sensitivity profile of Ukrain was comparable to that of the C. majus L. alkaloids, and different from that of thioTEPA, cyclophosphamide, etoposide and doxorubicin. Overall, doxorubicin was the most cytotoxic drug followed by cyclophosphamide. Ukrain and the C. majus L. alkaloids were slightly more cytotoxic than etoposide, while thioTEPA showed the lowest cytotoxicity. Co-exposure of thioTEPA with C. majus L. alkaloids resulted in additive but not in synergistic cytotoxicity. The in-vitro results indicate that the cytotoxicity of Ukrain against Ewing tumors is comparable to that of etoposide. While the latter can be used on the basis of broad clinical experience and known risk-benefit ratio, Ukrain for the present might be considered as a candidate for subsequent drug development by xenograft studies followed by systematic clinical trials.

PMID: 17001175 [PubMed - indexed for MEDLINE]





Int J Radiat Biol. 2002 Jan;78(1):17-27.
Ukrain, an alkaloid thiophosphoric acid derivative of Chelidonium majus L. protects human fibroblasts but not human tumour cells in vitro against ionizing radiation.

Cordes N, Plasswilm L, Bamberg M, Rodemann HP.
Section of Radiobiology and Molecular Environmental Research, Eberhard-Karls-University Tüebingen, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany.
PURPOSE: Ukrain, an alkaloid thiophosphoric acid derivative of Chelidonium majus L., has demonstrated a promising impact on chemotherapy in a variety of malignancies. The effects of the drug on cell survival, alteration of the cell cycle and induction of apoptosis were examined without and in combination with ionizing radiation (IR). The TP53 status of the cell lines used was also investigated. MATERIALS AND METHODS: Exponentially growing human tumour cell lines MDA-MB-231 (breast), PA-TU-8902 (pancreas), CCL-221 (colorectal), U-138MG (glioblastoma), and human skin and lung fibroblastic cells, HSF1, HSF2 and CCD32-LU were studied by colony assay, flow cytometry (cell-cycle, annexin-V staining for apoptosis) and Western blotting. Ukrain was used in concentrations from 0.1 to 50 microg ml(-1) for 1, 3 and 24 h and radiation as single doses of 1-10Gy. Combined drug-radiation exposure employed 1 microg ml(-1) Ukrain for 24h plus 2-8 Gy. RESULTS: Ukrain cytotoxicity was time- and dose-dependent. The combination of Ukrain plus IR gave enhanced toxicity in CCL-221 and U-138MG cells, but not in MDA-MB-231 and PA-TU-8902 cells. Most strikingly, a radioprotective effect was found in normal human skin and lung fibroblasts. Flow-cytometry analyses supported the differential and cell line-specific cytotoxicity of Ukrain. CCL-221 and U-138MG cells accumulated in G2 after 24-h Ukrain treatment, whereas no alterations were detected in the other tumour cells and normal fibroblasts tested. Western blotting of TP53 demonstrated non-functional overexpression in all tumour cell lines without affecting p21. HSF1 presented wild-type TP53 and a p21 response after IR. Flowcytometric analyses of annexin-V staining showed no induction of apoptosis after Ukrain treatment in comparison with untreated controls. CONCLUSIONS: Differential effects of Ukrain in modulating radiation toxicity of human cancer cell lines and its protective effect in normal human fibroblasts suggest that this alkaloid may have potential properties for clinical radiochemotherapy.

PMID: 11747550 [PubMed - indexed for MEDLINE]





Biomed Khim. 2008 May-Jun;54(3):289-300.
[Changes in amino acid patterns of blood plasma in tumor patients treated with anticancer drug NSC-631570: possible approaches to cancer diagnostics]

[Article in Russian]
Glazev AA, Nefedov LI.
In our early experimental (with W-256, SM-1 and PC-1 tumors) and clinical (breast, bladder and prostate cancers) studies the use of the anticancer drug NSC-631570 was proven to be safe and highly effective, inhibiting protein synthesis in cancer cells, selectively accumulating in cancer tissue after a single intravenous administration and controlling cancer-induced metabolic imbalance. This drug inhibits metabolic processes in the tumor and causes metabolic disorders in cancer cells. Moreover, NSC-631570 induced the changes in certain amino acids concentrations in biological fluids and tumor tissue in animal models and cancer patients. These changes cannot be explained by metabolic amino acid disorders in cancer known so far. In this study the effects of NSC-631570 on blood plasma amino acids has been investigated. Blood was sampled from 10 healthy donors and 29 patients with different types of cancer (stomach, rectal, lung, breast, bladder, prostate, and leukemia). Comparison of NSC-531570 effects in plasma of healthy donors and cancer patients has shown, that this compoumd: 1) affects amino acids with positively charged (His, Arg) or not charged (Tyr, Thr, Gln) R-groups; 2) decreases concentration of His and increase the concentrations of beta-Ala and Tau. These changes depend on the concentration of NSC-631570 and the type of cancer. On the basis of the literature data and the results of our studies we suggest that Ukrain's biological actions in cancer are realized at least partly through selective interaction with amino acids, their derivatives, and plasma proteins. These data provide the background for the using Ukrain in the cancer detection and investigating the mechanisms of carcinogenesis.

PMID: 18712085 [PubMed - indexed for MEDLINE]








BMC Cancer. 2006 Jan 17;6:14.
Proapoptotic activity of Ukrain is based on Chelidonium majus L. alkaloids and mediated via a mitochondrial death pathway.

Habermehl D, Kammerer B, Handrick R, Eldh T, Gruber C, Cordes N, Daniel PT, Plasswilm L, Bamberg M, Belka C, Jendrossek V.
Department of Radiation Oncology, University Hospital of Tuebingen, Hoppe-Seyler-Str. 3, D-72076 Tuebingen, Germany. daniel.habermehl@med.uni-tuebingen.de
BACKGROUND: The anticancer drug Ukrain (NSC-631570) which has been specified by the manufacturer as semisynthetic derivative of the Chelidonium majus L. alkaloid chelidonine and the alkylans thiotepa was reported to exert selective cytotoxic effects on human tumour cell lines in vitro. Few clinical trials suggest beneficial effects in the treatment of human cancer. Aim of the present study was to elucidate the importance of apoptosis induction for the antineoplastic activity of Ukrain, to define the molecular mechanism of its cytotoxic effects and to identify its active constituents by mass spectrometry. METHODS: Apoptosis induction was analysed in a Jurkat T-lymphoma cell model by fluorescence microscopy (chromatin condensation and nuclear fragmentation), flow cytometry (cellular shrinkage, depolarisation of the mitochondrial membrane potential, caspase-activation) and Western blot analysis (caspase-activation). Composition of Ukrain was analysed by mass spectrometry and LC-MS coupling. RESULTS: Ukrain turned out to be a potent inducer of apoptosis. Mechanistic analyses revealed that Ukrain induced depolarisation of the mitochondrial membrane potential and activation of caspases. Lack of caspase-8, expression of cFLIP-L and resistance to death receptor ligand-induced apoptosis failed to inhibit Ukrain-induced apoptosis while lack of FADD caused a delay but not abrogation of Ukrain-induced apoptosis pointing to a death receptor independent signalling pathway. In contrast, the broad spectrum caspase-inhibitor zVAD-fmk blocked Ukrain-induced cell death. Moreover, over-expression of Bcl-2 or Bcl-xL and expression of dominant negative caspase-9 partially reduced Ukrain-induced apoptosis pointing to Bcl-2 controlled mitochondrial signalling events. However, mass spectrometric analysis of Ukrain failed to detect the suggested trimeric chelidonine thiophosphortriamide or putative dimeric or monomeric chelidonine thiophosphortriamide intermediates from chemical synthesis. Instead, the Chelidonium majus L. alkaloids chelidonine, sanguinarine, chelerythrine, protopine and allocryptopine were identified as major components of Ukrain. Apart from sanguinarine and chelerythrine, chelidonine turned out to be a potent inducer of apoptosis triggering cell death at concentrations of 0.001 mM, while protopine and allocryptopine were less effective. Similar to Ukrain, apoptosis signalling of chelidonine involved Bcl-2 controlled mitochondrial alterations and caspase-activation. CONCLUSION: The potent proapoptotic effects of Ukrain are not due to the suggested "Ukrain-molecule" but to the cytotoxic efficacy of Chelidonium majus L. alkaloids including chelidonine.

PMID: 16417634 [PubMed - indexed for MEDLINE]


Int J Radiat Biol. 2003 Sep;79(9):709-20.
Fibronectin and laminin increase resistance to ionizing radiation and the cytotoxic drug Ukrain in human tumour and normal cells in vitro.

Cordes N, Blaese MA, Plasswilm L, Rodemann HP, Van Beuningen D.
Institute of Radiobiology, German Armed Forces Medical Academy, Neuherbergstrasse 11, D-80937 Munich, Germany. nils_cordes@web.de
PURPOSE: Cell-extracellular matrix (ECM) interactions are thought to mediate drug and radiation resistance. Dependence of cell survival, beta1-integrin expression and cell cycling on the ECM proteins and beta1-integrin ligands fibronectin (FN) and laminin (LA) were examined in malignant and normal cells exposed to the cytotoxic drug Ukrain plus/minus irradiation. MATERIALS AND METHODS: Human A549 lung cancer and MDAMB231 (MDA231) breast cancer cells and normal fibroblasts (HSF1) grown on FN, LA, bovine serum albumin (BSA) or polystyrene were treated with Ukrain (1 microg ml(-1), 24 h) plus/minus irradiation (2-8 Gy) and the effects studied using colony formation assays, flow cytometry (beta1-integrin, DNA analysis) and adhesion assays. RESULTS: FN and LA reduced the cytotoxic effect of single Ukrain treatment compared with polystyrene and BSA. FN and LA also abolished Ukrain-dependent radiosensitization in A549 cells and decreased the radiosensitivity of MDA231 and HSF1 cells. Single Ukrain exposure on polystyrene significantly reduced beta1-integrin expression and promoted G2-phase accumulation of A549 cells. In contrast, Ukrain-treated MDA231 and HSF1 cells showed elevated beta1-integrin expression and no Ukrain-specific cell cycle effect. Under Ukrain-radiation exposure, irradiation, FN or LA abolished Ukrain-mediated reduction of beta1-integrin expression and G2-phase accumulation in A549 cells, whereas in MDA231 cells and fibroblasts beta1-integrin expression and cell cycle distribution were stabilized. Cell adhesion to FN or LA was significantly impaired (A549) or improved (MDA231, HSF1) upon Ukrain treatment. CONCLUSIONS: The data corroborate the findings of other groups that cell adhesion-mediated resistance to either single or combined drug and radiation exposure is tightly correlated to specific ECM proteins. By demonstrating a strong modulatory impact of FN and LA on the radiosensitivity-modifying activity of the drug Ukrain, the set findings are also highly important for the assessment of drug and radiation effects within in vitro cytotoxicity studies. The data give the first mechanistic insights into specific FN- and LA-modulated cellular resistance mechanisms as well as into the important role for beta1-integrins using the unique cytotoxic and radiosensitivity-modifying drug Ukrain.

PMID: 14703944 [PubMed - indexed for MEDLINE]



Drugs Exp Clin Res. 2000;26(5-6):317-20.
Ukrain (NSC-631570) influences on bone status: a review.

Jabłoński M.
Medical University Orthopedic Department, Lublin, Poland. furjab@rubikon.net.pl
Ukrain, a thiophosphoric acid alkaloid derivative of Chelidonium majus L., was shown to affect bone tissue metabolism as assessed in densitometric and biomechanical studies in rats. Its action could be slightly osteopenic at the highest doses administered to intact animals for a prolonged period of time. This phenomenon is possibly related to Ukrain's inhibitory effect on spontaneous locomotor activity of treated animals and/or to the stimulatory effect of the drug on the osteoclastic activity via the macrophage system. By far, the most important finding seems to be the anabolic effect of Ukrain on bone in ovariectomized rats, which is most probably related to induced increase in the production of gonadal hormones, predominantly estrogens. In this regard, the postmenopausal population of female patients treated for malignancies with Ukrain (and obviously the most numerous one) meritis clinical attention as far as the antiosteoporotic effects of this drug are concerned.

PMID: 11345045 [PubMed - indexed for MEDLINE]



Cancer Biol Ther. 2006 Jul;5(7):788-93. Epub 2006 Jul 26.
NF-kappaB does not influence the induction of apoptosis by Ukrain.

Mendoza J, Zamora R, Gallardo JC, Ceballos G, Aldana A, Espinosa M, Maldonado V, Melendez-Zajgla J.
Molecular Biology Laboratory, Subdireccion de Investigacion Basica, Instituto Nacional de Cancerologia, Mexico City, Mexico.
Ukrain is a reaction product of different alkaloids from Chelidonium majus L. (celandine) conjugated with thiophosphoric acid. It has immunoregulatory effects on T lymphocyte subsets and cytotoxic and cytostatic effects on various malignant cells. Although Ukrain has been reported to induce alterations in the cell cycle and tubulin polymerization, the specific cellular target has not been described. Since antineoplasic agents induce NF-kappaB and their effects are regulated by this transcription factor, we investigated its possible participation in the apoptotic effects of Ukrain. Ukrain induced apoptosis in a panel of cancer cell lines by activating the intrinsic cell death pathway, as demonstrated by the cleavage of caspase 9 and the upregulation and cleavage of caspase 3. The effect was reversible, since long exposures (24 hours or more) were needed, as verified by clonogenic assays. Gene reporter assays showed that Ukrain activated NF-kappa B. Nevertheless, this activation was not required for, and did not modulate, the Ukrain effect: neither blockage of activation by a dominant negative version of Ikappa-B alpha or a Bcl-3 siRNA, nor activation of the pathway by overexpression of IKK2, changed the response to the drug. In conclusion, Ukrain induced apoptosis in HeLa cervical cancer cells by activating the intrinsic pathway. In contrast to other antineoplasic drugs, the effects of Ukrain were not regulated by NF-kappa B.

PMID: 16721042 [PubMed - indexed for MEDLINE]
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