Written by Katja Boehm, Edzard Ernst and the CAM-Cancer Consortium.
Updated February 28, 2017

Ukrain

What is it?

Ukrain (NSC-631570) is claimed to be a semisynthetic compound of thiophosphoric acid (triaziridide) and the alkaloid chelidonine derived from the common weed, Chelidonium majus (greater celandine), which grows primarily in Europe and Asia.1

Ingredients/Components

Ukrain has been described as a semi-synthetic Chelidonium majus alkaloid derivative, consisting of three chelidonine alkaloids combined to triaziridide. Panzer et al found the actions of Ukrain to be similar to the Chelidonium majus alkaloids it is prepared from.2

Chelidonium majus contains a range of more than 30 alkaloids, most notably isochinolin derivatives (chelidonine, coptisine, berberin etc.). Chemical analyses of Ukrain were inconsistent with the proposed trimeric structure and demonstrated that at least some commercial preparations of Ukrain consist of a mixture of C. majus alkaloids (including chelidonine).2

Serious doubts have been voiced concerning the chemical purity of the allegedly semi-synthetic mixed preparation from alkaloids of Chelidonium majus L and thiotepa.3 Thiotepa is a chemotherapy drug and cancer chemotherapeutic member of the alkylating agent group and is derived from aziridine and thiophosphoryl chloride and its main toxicity is myelosuppression.4 No thiotepa was contained in the Ukrain sample they investigated. Nowicky later on also claimed that the free thiotepa is removed out of the compound and that what is left is the Ukrain molecule and parts of the Chelidonium extract.5

Application and dosage

Ukrain is most commonly administered intravenously. It is claimed that it consists of one molecule of thiophosphoric acid conjugated to three molecules of chelidonine.

History / providers

Ukrain was developed in 1978 by Dr. Wassil J. Nowicky, director of the Ukrainian Anti-Cancer Institute of Vienna, Austria and first presented at the 13th International Congress of Chemotherapy in Vienna in August 1983. In 2004 and 2006, Nowicky was nominated for the Nobel Prize in Chemistry. The manufacturer of Ukrain is Nowicky Pharma, A-1040 Vienna, Austria.

Claims of efficacy / mechanisms of action / alleged indication

Several reports describe Eastern European clinical trials using Ukrain for people with various types of cancer.6 The mechanism of action of Ukrain is unknown whereas the mechanism of action of thiotepa is known. The drug works by damaging the DNA of cells, leaving the cell unable to divide.

Proposed activity of Ukrain includes cytotoxicity from effects on cellular oxygen consumption, inhibition of DNA, RNA, and protein synthesis, and induction of apoptosis. In vitro studies demonstrate weak inhibition of tubulin polymerization causing arrest at G2/M phase of the cell cycle. Limited in vitro data support the claim that Ukrain has selective cytotoxicity against cancer cells. Ukrain also is promoted for its claimed ability to increase total T-cell count and T-helper lymphocytes, while decreasing T-suppressor cells. In vitro activation of splenic lymphocytes also was reported.2,7,8

Antineoplastic and immunomodulatory effects have been suggested. For instance it has been suggested that the alkaloids interfering with the metabolism of cancer cells diminish synthesis of DNA, RNA and proteins. It has also been suggested that cellular oxygen consumption may be inhibited and thus a programmed cell death of malignant cells is thought to be induced.9

The antimitotic actions of Ukrain have been found to be reversible in low doses in vitro.10 They suggest that the lack of adverse effects observed in vivo may be due to the lack of therapeutically effective dosages being administered, therefore enabling cells to overcome the metaphase arrest and survive.

Various claims of efficacy of Ukrain exist, which have so far not been backed up by compelling scientific evidence. For instance, the producer of Ukrain claims that:11

  • It is toxic against cancer cells at the therapeutic dose but not against healthy cells.
  • It accumulates at the site of the tumour very rapidly after injection and brings about the encapsulation of larger tumours through anti-angiogenesis, thereby increasing operability.
  • It regenerates the immune system.

Prevalence of use

No data exist to estimate the prevalence of use of Ukrain by cancer patients.

Legal issues

Ukrain has no drug approval in the EU. In the UK, Ukrain neither has a marketing authorisation nor is it registered under the ‘traditional use’ label. It is not FDA-approved in the US but is approved in Mexico, and the United Arab Emirates as a standard anticancer medication. According to the manufacturer, NSC 631570 (=Ukrain) has drug licences in several states of the former Soviet Union (Ukraine, Georgia, Turkmenistan, Belarus/White Russia, Azerbaijan Republic, Tadshikistan, and the Ukraine. Ukrain has also been designated as an Orphan Drug for pancreatic cancer in the USA and in Australia.12

Dr Wassil Nowicky has submitted complaints to the European Court of Human Rights on account of “unlawful rejection of an approval application”.13

Costs and expenditures

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.14 For ten intravenous injections of 10-20 mg the total cost of medication itself is approximately (€2,900). This includes shipping, handling, bank transfer and prescription.

Citation

Katja Boehm, Edzard Ernst, CAM-Cancer Consortium. Ukrain [online document]. http://cam-cancer.org/The-Summaries/Herbal-products/Ukrain. February 28, 2017.

Document history

Assessed as up to date in February 2017 by Barbara Wider.
Assessed as up to date in January 2015 by Barbara Wider.
Assessed as up to date in August 2013 by Barbara Wider.
Most recent update and revision in May 2012 by Katja Boehm.
Fully revised and updated in July 2009 by Katja Boehm.
Summary first published in November 2005, authored by Katja Boehm and Edzard Ernst.

References

  1. Weiss RF. Herbal Medicine. Gothenburg, Sweden: Ab Arcanum and Beaconsfield, UK: Beaconsfield Publishers Ltd, 1985, 84–8.
  2. Panzer A, Hamel E, Joubert AM, Bianchi PC, Seegers JC. Ukrain (TM), a semisynthetic Chelidonium majus alkaloid derivative, acts by inhibition of tubulin polymerization in normal and malignant cell lines. Cancer Lett 2000;160(2):149-57.
  3. Panzer A, Joubert AM, Eloff JN, Albrecht CF, Erasmus E, Seegers JC. Chemical analyses of Ukrain, a semi-synthetic Chelidonium majus alkaloid derivative, fail to confirm its trimeric structure. Cancer Lett. 2000;160(2):237-41.
  4. van Maanen MJ, Huitema AD, Rodenhuis S, Beijnen JH. "Urinary excretion of thioTEPA and its metabolites in patients treated with high-dose cyclophosphamide, thioTEPA and carboplatin". Anticancer Drugs 2001;12 (6): 519–24.
  5. US 2006/0154947 A1 (2006-06-13) Wassyl Nowicky, Quaternary chelodine and alkaloid derivates, processes for their preparation and their use in manufacture of medicaments. [Patent]
  6. Susak YM, Zemskov VS, Yaremchuk OY, et al. Comparison of chemotherapy and x-ray therapy with Ukrain monotherapy for colorectal cancer. Drugs Exptl Clin Res 1996;22:115–22.
  7. Uglyanitsa KN, Nefyodov LI, Doroshenko YM, Nowicky JW, Volchek IV, Brzosko WJ, Hodysh YJ. Ukrain: a novel antitumour drug. Drugs Exp Clin Res 2000;56:347-56.
  8. Colombo ML, Bosisio E. Pharmacological activities of Chelidonium majus L. (papaveracea). Pharmacol Res 1996;33:127-34.
  9. Jagiello-Wojtowicz E, Kleinrok Z, Urbanska EM. Ukrain (NSC-631570) in experimental and clinical studies: a review. Drugs Exp Clin Res 1998;24:213-9.
  10. Panzer A, Joubert AM, Bianchi PC, Seegers JC. The antimitotic effects of Ukrain, a Chelidonium majus alkaloid derivative, are reversible in vitro. Cancer Lett. 2000;150(1):85-92.
  11. http://www.ukrin.com, accessed 28 February 2017.
  12. http://www.open-cc.com/English/1_04.asp, accessed 28 February 2017.
  13. http://ukrin.com/en/european-court, accessed 28 February 2017.
  14. Hopf G. Ukrain® - Fortschritt oder Rückschritt in der medikamentösen Therapie onkologischer Erkrankungen? Deutsche Zeitschrift für Onkologie 2002;34:31-6.
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  16. Susak YM, Yaremchuk OY, Zemskov VS, Kravchenko OB, Liepins A, Yatsyk IM et al. Randomised clinical study of Ukrain on colorectal cancer. Eur J Cancer 1995;31:S153 Abstract 733.
  17. Susak YM, Zemskov SV, Yaremchuk OY, Kravchenko OV, Yatsyk IM, Korsh OB. Comparison of chemotherapy and X-ray therapy with Ukrain monotherapy for colorectal cancer. Drugs Exp Clin Res 1996;22:115-22.
  18. Bondar GV, Borota AV, Yakovets YI, Zolotukhin SE. Comparative evaluation of the complex treatment of rectal cancer patients (chemotherapy and X-ray therapy, Ukrain monotherapy). Drugs Exp Clin Res 1998;24:221-6.
  19. Uglyanitsa KN, Nechiporenko NA, Nefyodov LI, Brzosko WJ. Ukrain therapy of stage T1NOMO bladder cancer patients. Drugs Exp Clin Res 1998;24:227-30.
  20. Zemskov VS, Procopchuk OL, Susak YM, Zemskov SV, Hodysh YY, Zemskova MV. Ukrain (NSC-631570) in the treatment of pancreas cancer. Drugs Exp Clin Res 2000;26:179-90.
  21. Uglyanitsa KN, Nefyodov LI, Brzosko WJ. Comparative evaluation of the efficiency of various Ukrain doses in the combined treatment of breast cancer. Report I. Clinical aspects of Ukrain application. Drugs Exp Clin Res 2000;26:223-30.
  22. Zemskov SV, Prokopchuk O, Susak Y, Zemskov S, Tkachenko O, Hodysh Y et al. Efficacy of Ukrain in the treatment of pancreatic cancer. Langenbecks Arch Surg 2002;387:84-9.
  23. Gansauge F, Ramadani M, Pressmar J, Gansauge S, Muehling B, Stecker K, Cammerer G, Leder G, Beger HG. NSC-631570 (Ukrain) in the palliative treatment of pancreatic cancer. Results of a phase II trial. Langenbecks Arch Surg 2002;386:570-4.
  24. Arzneimittelbrief. Phase-II-Studie zur Behandlung des fortgeschrittenen, inoperablen Pankreaskarzinoms mit Ukrain. AMB 2002;(5):39a.
  25. Der Spiegel (20. September 2008). Berühmter Chirurg soll wissenschaftliche Studien manipuliert haben. Spiegel 39/2008.
  26. Aschhoff B. Retrospective study of Ukrain treatment in 203 patients with advanced-stage tumors. Drugs Exptl Clin Res 2000;25:249-52.
  27. Gansauge F, Ramadani M, Schwarz M, Beger HG, Lotspeich E, Poch B. The clinical efficacy of adjuvant systemtic chemotherapy with gemcitabine and NSC-631570 in advanced pancreatic cancer. Hepato-Gastroenterology 2007;54:917-20.
  28. Prokopchuk OL, Zemskov SV, Susak YM. Ukrain treatment in a patient with metastatic renal cell carcinoma extending to the vena cava inferior. Case report. Drugs Exp Clin Res 2000;26:257-9.
  29. Prokopchuk OL, Zemskov SV, Susak YM. Ukrain treatment of a patient with retroperitoneal synovial sarcoma. Case report. Drugs Exp Clin Res 2000;26:255-6.
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  34. Susak YM, Skivka LM, Rudik MP, Pozur VV, Liubunya AV, Susak YM et al. Comparative investigation of the effect of Ukrain on growth of ascite and solid forms of Ehrlich's carcinoma. Experimental Oncology 2010; 32(2):107-110.
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  36. Funel N, Costa F, Pettinari L, Taddeo A, Sala A, Chiriva-Internati M et al. Ukrain affects pancreas cancer cell phenotype in vitro by targeting MMP-9 and intra-/extracellular SPARC expression. Pancreatology 2010; 10(5):545-552.
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