Scorpion Venom

Health Care Professional Information

Scientific Name
Rhopalurus junceus; other species include Mesobuthus martensii (Buthus martensii), Tityus cambridgei, Odontobuthus doriae, Tityus discrepans, Mesobuthus eupeus, Leiurus quinquestriatus, and Androctonus crassicauda
Common Name

Blue scorpion; other types include Chinese scorpion (Manchurian scorpion), Brazilian scorpion, Amazonian scorpion, Yellow Iranian scorpion, Venezuelan scorpion, Israeli scorpion, and Arabian fat-tailed scorpion

Brand Name

Escozul®, Vidatox®, Escozine® (all R. junceus-derived)

Clinical Summary

The scorpion is a predatory arthropod represented by more than 1500 different species worldwide (1). A part of the diverse arachnid class, scorpions possess a venomous stinger at the end of their tails used to paralyze prey or for self-defense. Although the venom is generally considered poisonous, there are varying degrees of pathogenicity and only a small fraction of scorpion species are deadly to humans (2).

The belief that scorpions have medicinal properties has existed for centuries, and many instances of their use have been recorded in both indigenous and folk medicine. In Traditional Chinese Medicine, the entire scorpion of the Buthus martensii Karsch (BmK) species is used to treat convulsions, spasms, and pain (3), and some laboratory studies confirm that scorpion venoms do contain antinociceptive properties (4) (5).

Scorpion venom has also been evaluated for other applications. It appears useful in killing intraerythrocytic malarial pathogens without harming the erythrocyte (6), and some species contain antimicrobial peptides that appear effective against yeast, fungi, bacteria, and viruses (7) (8). Scorpion venom could also be a source for the isolation of anticancer molecules. Preliminary assessments indicate that Tityus discrepans, Androctonus crassicauda, and Odontobuthus doriae venoms are effective inducers of apoptosis in breast cancer cell lines (9) (10) (11) . A component in BmK venom inhibits proliferation of human leukemia cells suggesting therapeutic potential in hematopoietic malignancies (12). Because the general composition and expression level of scorpion venom depends on genetic variations and geographical environments, research to identify the active components that have therapeutic potential across the various species continues (12) (13) (14).

Rhopalurus junceus, or blue scorpion venom, originated from Cuba, and is often marketed as having anticancer, anti-inflammatory, and analgesic properties. Claims for these products, known as Escozine and Escozul, are largely based on anecdotal information, testimonials, and preclinical experiments on laboratory animals. However, the manufacturers’ research cannot be corroborated and has not been published in any peer-reviewed journal (15) (16). In 2009, the Cuban government formally rejected the use of Escozul due to insufficient clinical data (17). Only recently has there been a functional characterization of R. junceus in the literature, but without any clinical evidence presented for R. junceus-derived products (18). A homeopathic version, Vidatox, has since been developed and has also not been evaluated in peer-reviewed journals.

The more likely scenario for future benefits with scorpion venom in cancer therapy may come from clinical trials involving chlorotoxin (CTX), a scorpion venom-derived peptide. CTX may facilitate the entry of chemotherapeutic compounds into tumor cells to target drug delivery and improve efficacy (19) (20) (21). In addition, it holds the potential for reducing side effects and can be synthesized in the laboratory (22). A synthetic CTX that selectively binds to glioma and other tumors cells is being evaluated as a radiopharmaceutical to deliver therapeutic levels of radiation directly to disease sites (23) (24). A CTX/near-infrared fluorescent molecule combination is under investigation as a cancer imaging agent, a kind of “tumor paint” that may help surgeons more clearly identify tumor margins and micrometastases, and spare normal tissue (25) (26) (27).

Continued research on the complex characteristics of scorpion venom among the various species is needed to both isolate the properties of therapeutic importance and develop their application in cancer research.

Purported Uses
  • Analgesic
  • Anti-inflammatory
  • Cancer treatment
  • Chemotherapy side effects
  • Radiation side effects
Constituents

Varies according to several factors including species, geography, and environmental conditions (12) (14)

General
• Proteins: neurotoxic peptides [ion channel toxins (Na+, K+, Ca2+), chlorotoxin]; antinociceptive peptides (4)
• Enzymes: acetylcholinesterase, phospholipase A2, hyaluronidase, alkaline phosphatase, proteolytic enzymes
• Enzyme inhibitors
• Nucleotides
• Lipids
• Mucopolysaccharides
• Biogenic amines: histamines, serotonin
(11) (14) (28) (29) (30)

R. junceus (blue scorpion) soluble venom
At least 50 components, including (18):
• Enzymes (phospholipase, hyaluronidase)
• Antimicrobials similar to other scorpion venoms
• Venom peptides: RjAa12f, a component similar to insect toxins in other scorpion venoms; Na+ and K+ ion channel components  

Mechanism of Action

The sheer number of compounds and their diverse pharmacologic properties among different scorpion species leaves their mechanisms poorly understood (12) (31). Most scorpion venoms are known to contain peptide toxins that mainly act on ion channels (29).

The venom from R. junceus was shown to have reversible beta and alpha activities. It enabled sodium channels to open at more negative potentials, delayed inactivation of potassium channels, and rapidly blocked ERG potassium channels in neuroblastoma cells (18). Proteins found in T. discrepans venom bind to FasL and Bcl-2 on the surface of breast cancer cells inducing apoptosis (9). BmK venom also induces apoptosis in human lymphoma cells by upregulating PTEN, and decreases levels of Akt and Bad phosphorylation, resulting in increased p27 expression (32). Another component of BmK venom inhibits cell proliferation by modulating NF-κB activation in human leukemia cells (12). A. crassicauda and O. doriae venoms induce apoptosis via caspase-3 activity and nuclear DNA fragmentation in neuroblastoma and breast cancer cells (10) (11). Further, the proteolytic enzymes in scorpion venom are likely responsible for its necrotic activity (11). Leiurus quinquestriatus venom contains a chlorotoxin (CTX) associated with matrix metalloproteinase-2 that increases its affinity for primary brain tumors and reduces the potential for tumor invasion of healthy tissue (20) (21). CTX, which functions as a paralytic in nature, has a molecular structure with a single tyrosine residue available for radioiodination (33). Synthetic CTX has shown antiangiogenic properties and a synergistic effect with bevacizumab in animal models (24) and specifically binds with the protein annexin A2 in diverse tumor cell lines (34).

An array of other components in scorpion venoms may have therapeutic uses. BmK venom has sympathomimetic and analgesic properties (30) (35). It contains a peptide that modulates G-protein-coupled receptor activity, and has a primary structure similar to enkephalin-like peptides (31). Other venoms also exhibit antinociceptive properties which appear to be activated by an endogenous opioid system partly triggered by counterirritation (5).

Adverse Reactions

The venoms marketed to cancer patients currently remain untested and unregulated by health authorities. A lack of documentation on side effects does not preclude the potential for adverse events.

Adverse events with respect to isolated substances being developed for clinical studies are also yet to be determined.

Herb-Drug Interactions

Anticonvulsants: Theoretical interaction due to anticonvulsant properties (3).
Sympathomimetics: Theoretical interaction due to sympathomimetic properties (30).

Herb Lab Interactions

Scorpion venom could potentially alter prothrombin time, partial prothrombin time, and international normalized ratio values due to presence of phospholipase A2 (11).

Dosage (Inside MSKCC Only)
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References
  1. Dabo A, Golou G, Traore MS, et al. Scorpion envenoming in the north of Mali (West Africa): epidemiological, clinical and therapeutic aspects. Toxicon. Aug 2011;58(2):154-158.
  2. de Roodt AR, Garcia SI, Salomon OD, et al. Epidemiological and clinical aspects of scorpionism by Tityus trivittatus in Argentina. Toxicon. Jun 2003;41(8):971-977.
  3. Zhao R, Weng CC, Feng Q, et al. Anticonvulsant activity of BmK AS, a sodium channel site 4-specific modulator. Epilepsy Behav. Feb 2011;20(2):267-276.
  4. Wang Y, Hao Z, Shao J, et al. The role of Ser54 in the antinociceptive activity of BmK9, a neurotoxin from the scorpion Buthus martensii Karsch. Toxicon. Nov 2011;58(6-7):527-532.
  5. Martin-Eauclaire MF, Abbas N, Sauze N, et al. Involvement of endogenous opioid system in scorpion toxin-induced antinociception in mice. Neurosci Lett. Sep 20 2010;482(1):45-50.
  6. Gao B, Xu J, Rodriguez Mdel C, et al. Characterization of two linear cationic antimalarial peptides in the scorpion Mesobuthus eupeus. Biochimie. Apr 2010;92(4):350-359.
  7. Gao B, Sherman P, Luo L, et al. Structural and functional characterization of two genetically related meucin peptides highlights evolutionary divergence and convergence in antimicrobial peptides. FASEB J. Apr 2009;23(4):1230-1245.
  8. Chen Y, Cao L, Zhong M, et al. Anti-HIV-1 activity of a new scorpion venom peptide derivative Kn2-7. PLoS One. 2012;7(4):e34947.
  9. D'Suze G, Rosales A, Salazar V, et al. Apoptogenic peptides from Tityus discrepans scorpion venom acting against the SKBR3 breast cancer cell line. Toxicon. Dec 2010;56(8):1497-1505.
  10. Zargan J, Sajad M, Umar S, et al. Scorpion (Androctonus crassicauda) venom limits growth of transformed cells (SH-SY5Y and MCF-7) by cytotoxicity and cell cycle arrest. Exp Mol Pathol. Aug 2011;91(1):447-454.
  11. Zargan J, Umar S, Sajad M, et al. Scorpion venom (Odontobuthus doriae) induces apoptosis by depolarization of mitochondria and reduces S-phase population in human breast cancer cells (MCF-7). Toxicol In Vitro. Dec 2011;25(8):1748-1756.
  12. Song X, Zhang G, Sun A, et al. Scorpion venom component III inhibits cell proliferation by modulating NF-kappaB activation in human leukemia cells. Exp Ther Med. Jul 2012;4(1):146-150.
  13. Batista CV, Roman-Gonzalez SA, Salas-Castillo SP, et al. Proteomic analysis of the venom from the scorpion Tityus stigmurus: biochemical and physiological comparison with other Tityus species. Comp Biochem Physiol C Toxicol Pharmacol. Jul-Aug 2007;146(1-2):147-157.
  14. Batista CV, del Pozo L, Zamudio FZ, et al. Proteomics of the venom from the Amazonian scorpion Tityus cambridgei and the role of prolines on mass spectrometry analysis of toxins. J Chromatogr B Analyt Technol Biomed Life Sci. Apr 15 2004;803(1):55-66.
  15. Garcia AD, Diaz, L. M., Sanchez, H. R., Lorenzo, Y. C. Cytotoxicity of Rholopalurus junceus-Cuban scorpion venom and its fractionations on human tumor cell lines. LABIOFAM. Available at: http://revistas.labiofamcuba.com. Accessed November 6, 2012.
  16. Hernández Betancourt CH, Iglesias Huerta, et al. In vitro toxicity assessment caused by Rophalurus junceus scorpion poison though a cellular assay. Revista Cubana de Investigaciones Biomedicas. 2009;28:(1). Available at http://scielo.sld.cu. Accessed November 6, 2012.
  17. de la Osa J. Cuba releases cautionary article about Escozul cancer treatment from Cuba. Havana Journal. 2009. Available at: http://havanajournal.com. Accessed November 6, 2012.
  18. Garcia-Gomez BI, Coronas FI, Restano-Cassulini R, et al. Biochemical and molecular characterization of the venom from the Cuban scorpion Rhopalurus junceus. Toxicon. Jul 2011;58(1):18-27.
  19. Xiang Y, Liang L, Wang X, et al. Chloride channel-mediated brain glioma targeting of chlorotoxin-modified doxorubicine-loaded liposomes. J Control Release. Jun 30 2011;152(3):402-410.
  20. Deshane J, Garner CC, Sontheimer H. Chlorotoxin inhibits glioma cell invasion via matrix metalloproteinase-2. J Biol Chem. Feb 7 2003;278(6):4135-4144.
  21. Fu Y, An N, Li K, et al. Chlorotoxin-conjugated nanoparticles as potential glioma-targeted drugs. J Neurooncol. May 2012;107(3):457-462.
  22. Graf N, Mokhtari TE, Papayannopoulos IA, et al. Platinum(IV)-chlorotoxin (CTX) conjugates for targeting cancer cells. J Inorg Biochem. May 2012;110:58-63.
  23. Mamelak AN, Rosenfeld S, Bucholz R, et al. Phase I single-dose study of intracavitary-administered iodine-131-TM-601 in adults with recurrent high-grade glioma. J Clin Oncol. Aug 1 2006;24(22):3644-3650.
  24. Jacoby DB, Dyskin E, Yalcin M, et al. Potent pleiotropic anti-angiogenic effects of TM601, a synthetic chlorotoxin peptide. Anticancer Res. Jan 2010;30(1):39-46.
  25. Akcan M, Stroud MR, Hansen SJ, et al. Chemical re-engineering of chlorotoxin improves bioconjugation properties for tumor imaging and targeted therapy. J Med Chem. Feb 10 2011;54(3):782-787.
  26. Veiseh M, Gabikian P, Bahrami SB, et al. Tumor paint: a chlorotoxin:Cy5.5 bioconjugate for intraoperative visualization of cancer foci. Cancer Res. Jul 15 2007;67(14):6882-6888.
  27. Stroud MR, Hansen SJ, Olson JM. In vivo bio-imaging using chlorotoxin-based conjugates. Curr Pharm Des. Dec 2011;17(38):4362-4371.
  28. Petricevich VL. Scorpion venom and the inflammatory response. Mediators Inflamm. 2010;2010:903295.
  29. Goudet C, Chi CW, Tytgat J. An overview of toxins and genes from the venom of the Asian scorpion Buthus martensi Karsch. Toxicon. Sep 2002;40(9):1239-1258.
  30. Foucart S, Wang R, Moreau P, et al. Effects of Buthus martensii Karsch scorpion venom on the release of noradrenaline from in vitro and in vivo rat preparations. Can J Physiol Pharmacol. Aug 1994;72(8):855-861.
  31. Zhang Y, Xu J, Wang Z, et al. BmK-YA, an enkephalin-like peptide in scorpion venom. PLoS One. 2012;7(7):e40417.
  32. Gao F, Li H, Chen YD, et al. Upregulation of PTEN involved in scorpion venom-induced apoptosis in a lymphoma cell line. Leuk Lymphoma. Apr 2009;50(4):633-641.
  33. Mrugala MM, Adair JE, Kiem HP. Outside the box—novel therapeutic strategies for glioblastoma. Cancer J. Jan-Feb 2012;18(1):51-58.
  34. Kesavan K, Ratliff J, Johnson EW, et al. Annexin A2 is a molecular target for TM601, a peptide with tumor-targeting and anti-angiogenic effects. J Biol Chem. Feb 12 2010;285(7):4366-4374.
  35. Xiong YM, Lan ZD, Wang M, et al. Molecular characterization of a new excitatory insect neurotoxin with an analgesic effect on mice from the scorpion Buthus martensi Karsch. Toxicon. Aug 1999;37(8):1165-1180.

Consumer Information

How It Works

Bottom Line: Although components of scorpion venom from various species show anticancer effects in laboratory and animal studies, the scorpion venom marketed to cancer patients has not been scientifically proven to treat cancer in humans.

The claims made for blue scorpion venom marketed to cancer patients as Escozine, Escozul, and Vidatox (a homeopathic version) are mostly based on anecdotes, testimonials, and experiments which may or may not have been properly carried out. In Cuba where these products originated, the government rejected the use of Escozul in 2009 because they did not have enough data. The homeopathic version, which uses very dilute solutions of the active ingredient, has not been shown to treat or prevent cancer. The properties of blue scorpion venom are just starting to be described more thoroughly in scientific research. Therefore, like venoms from other scorpion species, blue scorpion venom compounds one day may be isolated and properly developed to create cancer therapies, but much more research is needed.

Purported Uses
  • Analgesic
    A few laboratory studies suggest that scorpion venom may be helpful in relieving pain, but human studies are lacking.
  • Anti-inflammatory
    No scientific evidence currently supports this use.
  • Cancer treatment
    No scientific evidence supports this use. The “scientific” papers published online about scorpion venom products have not been properly evaluated by the scientific community.
  • Chemotherapy side effects
    No scientific evidence currently supports this use.
  • Immunostimulation
    Laboratory studies indicate that scorpion venoms have properties that may be effective against various yeast, fungi, bacteria, and viruses. More studies are needed.
  • Radiation side effects
    No scientific evidence currently supports this use.
Patient Warnings

Scorpion venom products marketed to cancer patients including Escozine and Vidatox have not been studied in clinical trials. There is no evidence for their use to prevent or treat cancer in humans, and they have not been reviewed or approved by the FDA.

Side Effects

The venoms marketed to cancer patients are untested and unregulated by health authorities. Therefore side effects are currently unknown.

E-mail your questions and comments to aboutherbs@mskcc.org.