Ukrain

• How It Works

  Ukrain has not been shown to prevent or treat cancer, but may be useful as palliative care in some instances.

  Ukrain is an alkaloid extract from the plant Chelidonium majus, a common weed. It was developed over 20 years ago by a scientist from the Ukraine, who tested the product on patients with several different types of cancers. In lab experiments, Ukrain was found to kill cancer cells while leaving healthy cells alone. This may occur by disrupting changes in cell structure during cell division. Because cancer cells divide more rapidly than healthy cells, such a disruption could slow the growth of cancer cells, causing their death. Some lab experiments suggest that Ukrain may stimulate certain aspects of the immune system, but it is uncertain if these effects could occur in humans. Two small studies suggest Ukrain may be helpful for advanced pancreatic cancer patients, but additional studies are needed to confirm effects and safety.

• Purported Uses
  • To prevent and treat cancer
    Two small pilot studies suggest that Ukrain may be useful in the treatment of advanced pancreatic cancer, but there were also side effects that may be related to its use. More studies are needed to confirm safety and effects.
  • To treat hepatitis
    No scientific evidence supports this use.
  • To treat HIV and AIDS
    There are no data to back this claim.
  • To stimulate the immune system
    Although lab studies suggest that Ukrain stimulates the activity of certain immune cells, human data are lacking.
• Side Effects
  • Nausea
  • Soreness at injection site
  • Diarrhea
  • Dizziness
  • Fatigue
  • Drowsiness
  • Chronic excessive thirst
  • Excessive urination
  • Slight fever
  • Possible tumor bleeding, as reported in a small study
• Special Point

  Anecdotes suggest effectiveness in humans, but adequately controlled clinical trials have not been published. Ukrain™ is not approved by the Food and Drug Administration but is available in parts of Europe and from Tijuana clinics. Although the product labeling makes claims of effectiveness and safety, none of these claims have been sufficiently proven.

• Brand Name

  Ukrain™ (Nowicky Pharma, Vienna, Austria)

• Clinical Summary

  Ukrain™ is a semi-synthetic proprietary product derived from the common weed Chelidonium majus or greater celandine that contains alkaloids and thiophosphoric acid ^(1) (2). Patients use it to treat HIV/AIDS and hepatitis C, but it is mainly promoted as an alternative anticancer agent.

  In vitro data suggest that Ukrain may increase total T-cell count and T-helper lymphocytes, decrease T-suppressor cells, and activate splenic lymphocytes ^(3) (4). Antitumor effects in vitro and in animal studies have also been reported ^{(5) (6) (7) (8)}. In breast cancer and melanoma cells, Ukrain may have a synergistic effect when used with bortezomib ⁽⁹⁾. Preliminary studies in humans indicate it may be beneficial in the palliative care setting ⁽¹⁾ and prolong survival in pancreatic cancer patients when administered with gemcitabine ⁽¹⁰⁾. A systematic review of clinical trials also suggests it may have anticancer potential ⁽²⁾. Large-scale studies are needed to confirm this effect.

  Reported adverse effects include injection site reactions, slight fever, fatigue, dizziness, nausea, and possibly tumor bleeding.

  Ukrain™ is not approved by the Food and Drug Administration but is available in parts of Europe and from Tijuana clinics. Critics cite a lack of scientific rigor and independent evaluation to confirm efficacy and safety ^(2) (18).

• Purported Uses
  • Cancer prevention
  • Cancer treatment
  • Hepatitis
  • HIV and AIDS
  • Immunostimulation
• Mechanism of Action

  Proposed activity includes cytotoxicity from effects on cellular oxygen consumption, and inhibition of DNA, RNA, and protein synthesis. In vitro studies demonstrate weak inhibition of tubulin polymerization causing cell cycle arrest at the G2/M phase ⁽¹¹⁾. Proapoptotic effects are particularly attributed to alkaloid constituents including chelidonine ⁽¹²⁾. Constituents such as thiophosphoric acid and other derivatives may also contribute to its anticancer activities ^(2) (3). Ukrain switches epithelial–mesenchymal transitions in malignant renal cell carcinoma ⁽¹³⁾, and exerts an antiproliferative effect on pancreatic ductal adenocarcinoma cells by targeting mitotic spindle microtubules ⁽¹⁴⁾. In animal models, Ukrain restored pro-inflammatory functions of hypoxic macrophages ⁽¹⁵⁾.

• Adverse Reactions

  Parenteral administration: Soreness at injection site, nausea, diarrhea, dizziness, fatigue, drowsiness, polydipsia, polyuria, and slight fever.
  Hematological side effects and tumor bleeding were reported in a recent phase II trial.
  ^{(1) (3) (17)}

• References

  1. Gansauge F, Ramadani M, Pressmar J, et al. NSC-631570 (Ukrain) in the palliative treatment of pancreatic cancer. Results of a phase II trial. Langenbecks Arch Surg. Mar 2002;386(8):570-574. doi: 10.1007/s00423-001-0267-5

  2. Ernst E, Schmidt K. Ukrain – a new cancer cure? A systematic review of randomised clinical trials. BMC Cancer. 2005;5:69. doi: 10.1186/1471-2407-5-69

  3. Uglyanitsa KN, Nefyodov LI, Doroshenko YM, et al. Ukrain: a novel antitumor drug. Drugs Exp Clin Res. 2000;26(5-6):341-356.

  4. Colombo ML, Bosisio E. Pharmacological activities of Chelidonium majus L. (Papaveraceae). Pharmacol Res. Feb 1996;33(2):127-134. doi: 10.1006/phrs.1996.0019

  5. Skivka L, Susak Y, Trompak O, et al. The effect of monotherapy and combined therapy with NSC-631570 (ukrain) on growth of low- and high-metastasizing B16 melanoma in mice. J Oncol Pharm Pract. Dec 2011;17(4):339-349. doi: 10.1177/1078155210382470

  6. Skivka LM, Trompak OO, Kudryavets YI, et al. The effect of NSC-631570 (ukrain) alone and in combination with pathogen-associated molecules on cell cycle distribution and apoptosis induction of mouse melanoma cells with different biological properties. Exp Oncol. Jul 2010;32(2):92-96.

  7. Venkatesh K, Govindaraj S, Ramachandran A, et al. Effect of ukrain on cell survival and apoptosis in the androgen-independent prostate cancer cell line PC-3. J Environ Pathol Toxicol Oncol. 2011;30(1):11-19.

  8. Bozeman EN, Srivatsan S, Mohammadi H, et al. Ukrain, a plant derived semi-synthetic compound, exerts antitumor effects against murine and human breast cancer and induce protective antitumor immunity in mice. Exp Oncol. Dec 2012;34(4):340-347.

  9. Savran B, Yerlikaya A, Erdogan E, et al. Anticancer agent ukrain and bortezomib combination is synergistic in 4T1 breast cancer cells. Anticancer Agents Med Chem. Mar 2014;14(3):466-472.

  10. Gansauge F, Ramadani M, Schwarz M, et al. The clinical efficacy of adjuvant systemic chemotherapy with gemcitabine and NSC-631570 in advanced pancreatic cancer. Hepatogastroenterology. Apr-May 2007;54(75):917-920.

  11. Panzer A, Hamel E, Joubert AM, et al. Ukrain(TM), a semisynthetic Chelidonium majus alkaloid derivative, acts by inhibition of tubulin polymerization in normal and malignant cell lines. Cancer Lett. Nov 28 2000;160(2):149-157.

  12. Habermehl D, Kammerer B, Handrick R, et al. Proapoptotic activity of Ukrain is based on Chelidonium majus L. alkaloids and mediated via a mitochondrial death pathway. BMC Cancer. 2006;6:14. doi: 10.1186/1471-2407-6-14

  13. Gagliano N, Pettinari L, Aureli M, et al. Malignant phenotype of renal cell carcinoma cells is switched by ukrain administration in vitro. Anticancer Drugs. Sep 2011;22(8):749-762. doi: 10.1097/CAD.0b013e328346c7f7

  14. Gagliano N, Volpari T, Clerici M, et al. Pancreatic cancer cells retain the epithelial-related phenotype and modify mitotic spindle microtubules after the administration of ukrain in vitro. Anticancer Drugs. Oct 2012;23(9):935-946. doi: 10.1097/CAD.0b013e32835507bc

  15. Skivka LM, Fedorchuk OG, Rudyk MP, et al. Antineoplastic drug NSC631570 modulates functions of hypoxic macrophages. Tsitol Genet. Sep-Oct 2013;47(5):70-82.

  16. Jagiello-Wojtowicz E, Kleinrok Z, Chodkowska A, et al. Preliminary pharmacokinetic studies of Ukrain in rats. Drugs Exp Clin Res. 1998;24(5-6):309-311.

  17. Danysz A, Kokoschinegg M, Hamler F. Clinical studies of Ukrain in healthy volunteers (phase 1). Drugs Exp Clin Res. 1992;18 Suppl:39-43.

  18. Ponde N, Ades F, de Azambuja E. Threat posed by unproven drugs in medical oncology. ESMO Open. 2016;1(3):e000064.