The venom of the chactid Brotheas amazonicus may be used in cancer research and treatment

 

There have been a lot of research into scorpion venom to find potential agents to be used in medicine and treatment of serious diseases like cancer. Chlorotoxin from the venom of Leiurus quinquestriatus (Ehrenberg, 1828) (Buthidae) is one example of a very promising agent in the fight against serious brain cancer.

In a recent paper by Mouzarllem Barros Reis and co-workers, they studied the venom of the amazonian scorpion  Brotheas amazonicus Lourenço, 1988 (Chactidae). I'm not going into detail about this work as this is way outside my expertise, but just mention that the study demonstrates that venom of the this species contains a scorpine-like molecule with high cytolytic activity in human breast cancer tumor lines. This opens that possibility for using molecules from the venom into cancer research and therapy.

Abstract:
Introduction: Scorpion venoms contain bioactive molecules with potential antitumor properties. This study aimed to evaluate the cytotoxic effects of crude Brotheas amazonicus venom (BamazV) and its molecular weight–separated fractions on human breast cancer cell lines, with a focus on identifying active compounds and elucidating their mechanisms of action.
Methods: Human breast epithelial (MCF10A) and breast cancer cell lines (SKBR3, MCF7, and MDA-MB-231) were first assessed for dose-dependent responses to paclitaxel, a standard chemotherapeutic agent. BamazV was fractionated by ultrafiltration into >10 kDa, 3–10 kDa, and <3 kDa fractions, which were tested for cytotoxic activity. The active fraction underwent reversed-phase chromatography, and the major bioactive peptide was characterized by mass spectrometry and Edman degradation. Cytotoxic mechanisms were investigated using cell death assays.
Results: All cell lines showed a dose-dependent response to paclitaxel. Crude BamazV induced significant cytotoxicity at concentrations ≥ 50 μg/mL, with triplenegativeMDA- MB-231 cells being themost sensitive. The >10 kDa fraction retained cytotoxic activity, leading to the isolation of a major peptide, BamazScplp1. Sequence analysis revealed 46–55% identity and 74–81% similarity to known scorpine-like peptides. Functional assays indicated that BamazScplp1 induced predominantly necrotic cell death, consistent with the activity profile of previously reported cytolytic scorpine-like molecules.
Discussion: These findings identify BamazScplp1 as a scorpine-like peptide with selective cytotoxicity toward triple-negative breast cancer cells, underscoring the potential of B. amazonicus venom as a source of bioactive compounds for cancer research.

Reference:
Reis MB, Bordon KDCF, Martins JG, Wiezel GA, Cipriano U, Procopio REdL, et al. A novel scorpine-like peptide from the amazonian scorpion Brotheas amazonicus with cytolytic activity. Front Pharmacol. 2025;16:1652614. [Open Access]

Thanks to Jonas Martins for sending me their article!

Odontobuthus doriae venom as cancer medicine

Scorpions have been used in traditional medicine since ancient times, and in the last decade there have been a lot of research into scorpion venom to find potential agents to be used in medicine and treatment of serious diseases like cancer. Chlorotoxin from the venom of Leiurus quinquestriatus is one example of a very promising agent in the fight against serious brain cancer.

Jamil Zargan and co-workers have now showed that the venom of Odontobuthus doriae (Thorell, 1876) (Buthidae) induced apoptosis (programmed cell death) and inhibits DNA synthesis (inhibit cell growth and cell proliferation) in human neuroblastoma cells (Wikipedia on neuroblastoma). More investigations of the venom of this species are of course necessary, but the properties shown by the venom in this study will make it a valuable therapeutic agent in cancer research.

Abstract:
Scorpion and its organs have been used to cure epilepsy, rheumatism, and male impotency since medieval times. Scorpion venom which contains different compounds like enzyme and non-enzyme proteins, ions, free amino acids, and other organic inorganic substances have been reported to posses antiproliferative, cytotoxic, apoptogenic, and immunosuppressive properties. We for the first time report the apoptotic and antiproliferative effects of scorpion venom (Odontobuthus doriae) in human neuroblastoma cells. After exposure of cells to medium containing varying concentrations of venom (10, 25, 50, 100, and 200 lg/ml), cell viability decreased to 90.75, 75.53, 55.52, 37.85, and 14.30%, respectively, after 24 h. Cells expressed morphological changes like swelling, inhibition of neurite outgrowth, irregular shape, aggregation, rupture of membrane, and release of cytosolic contents after treatment with venom. Lactate dehydrogenase (LDH) level increased in 50 and 100 lg/ml as compared to control, but there was no significant increase in LDH level at a dose of 10 and 20 lg/ml. Two concentrations viz. 50 and 100 lg/ml were selected because of the profound effect of these concentrations on the cellular health and population. Treatment with these two concentrations induced reactive nitrogen intermediates and depolarization in mitochondria. While caspase-3 activity increased in a concentrationdependent manner, only 50 lg/ml was able to fragment DNA. It was interesting to note that at higher dose, i.e., 100 lg/ml, the cells were killed, supposedly by acute necrosis. DNA synthesis evidenced by bromodeoxyuridine (BrdU) incorporation was inhibited in a concentrationdependent manner. The cells without treatment incorporated BrdU with high affinity confirming their cancerous nature whereas very less incorporation was noticed in treated cells. Our results show apoptotic and antiproliferative potential of scorpion venom (O. doriae) in human neuroblastoma cells. These properties make scorpion venom a valuable therapeutic agent in cancer research.

Reference:
Zargan J, Sajad M, Umar S, Naime M, Ali S, Khan HA. Scorpion (Odontobuthus doriae) venom induces apoptosis and inhibits DNA synthesis in human neuroblastoma cells. Mol Cell Biochem. 2011 Feb;348(1-2):173-81. [Subscription required for fulltext]

Another Leiurus peptid may be important in fighting serious diseases

The venom of Leiurus quinquestriatus has been subjected to massive research in the last years. It has already been shown that a syntetic version the peptid Chlorotoxin (TM-601) binds to malignant brain tumor cells (gliomas) with high affinity and does not seem to bind to normal brain tissue. This ability has been promising in developing new treatment for this serious disease, and the first human trials have been conducted.

In a recent article in Journal of Biological Chemistry, an international research team describes a new peptid from Leiurus (GaTx1). This peptid controls the movement of ions and water out of cells by interacting with a crucial chlorid channel. This particular ability may be instrumental in developing treatment for the very serious disease cystic fibrosis, which affect more than 70 000 peoples worldwide.

A lot more research is of course neccessary before we know for sure that GaTx1 can be used in treating cystic fibrosis, but it is very interesting that what is belived to be the most venomous scorpion in the world also can save lives.

Read more about this story here:
Scorpion peptide may be key to secretory diseases

Original article:
Fuller, M.D., Thompson, C.H., Zhang, Z. R., Freeman, C.S., Schay, E., Szakacs, G., Bakos, E., Sarkadi, B., McMaster, D., French, R.J., Pohl, J., Kubanek, J. & McCarty, N. A. State-dependent inhibition of cystic fibrosis transmembrane conductance regulator chloride channels by a novel peptide toxin. Journal of Biological Chemistry. 2007. 282(52):37545-55 (Subscription required for fulltext).

Venom of two scorpion species can be used in developing drugs against the tropical disease Leishmaniasis

 

Scorpions and their venom is a goldmine when it comes to finding molecules and toxins that can be used to develop medicines and other useful products for humans. One of the most known examples is Chlorotoxin, a peptid found in the venom of Leiurus quinquestriatus (Ehrenberg, 1828) (Buthidae), which has been used in the development of methods for the treatment and diagnosis of several types of cancer. There is a huge amount of research on scorpion venom going on these days.

D. B. Pereiraa and co-workers recently published a study where they showed that the venoms of Brotheas amazonicus Lourenço, 1988 (Chactidae) and Tityus metuendus Pocock, 1897 (Buthidae) can be used in the fight against the tropical disease Leishmaniasis (a zonosis caused by parasites of the Trypanosomatida genus Leishmania). The authors hope that components in the venom can be used in the development of new drugs against this serious tropical disease.

Abstract:
Leishmaniasis is a vector-transmitted zoonosis caused by different species of the genus Leishmania, with a wide clinical spectrum. It is a public health problem aggravated by a series of limitations regarding treatment. In the search for new therapeutic alternatives, scorpion venoms are a source of multifunctional molecules that act against the natural resistance of pathogens. This work evaluated the antileishmanial potential of Brotheas amazonicus and Tityus metuendus venoms against the promastigote forms of Leishmania amazonensis e Leishmania guyanensis. The venoms of B. amazonicus and T. metuendus were evaluated for their constituents using Fourier Transform Infrared (FTIR). Growth inhibition and death of promastigotes were evaluated in the presence of diferente crude venom concentrations (100 μg/mL, 50 μg/mL, 10 μg/mL, 1 μg/mL) after one hour of incubation at 25 °C. The FTIR spectra of both venoms exhibited bands in approximate regions, revealing that both exhibit similar functional groups. Crude venom from both scorpion species showed similar or superior leishmanicidal effects to the standart drug N-methylglucamine antimoniate. At the highest concentration of 100 μg/mL, cultures of L. guyanensis treated with the venom of B. amazonicus showed the highest mortality percentages, above 28%, while T. metuendus venom showed the highest activity against L. amazonensis, with mortality above 7%. This preliminar study demonstrates that B. amazonicus and T. metuendus venoms can be important tools in the search for new drugs Against leishmaniasis. Next step involves evaluating the activity against the amastigote forms and purifying the venom proteins in order to identify the best anti-leishmania candidates.

Reference:
Pereira D, Martins J, Oliveira M, Lima-Júnior R, Rocha L, Andrade S, Procópio R. Leishmanicidal activity of the venoms of the Scorpions Brotheas amazonicus and Tityus metuendus. Brazilian Journal of Biology. 2023;83:e276872. [Open Access]

Thanks to Jonas Martin for sending me their article!

Antibiotic-producing bacteria discovered in tissue from the giant sand scorpion, Smeringurus mesaensis

 

As most of you know, there is an increasing and worrying number of treatment resistant bacteria in the world. It is probably safe to say that we are now in an antibiotic resistance crisis. The venom of scorpions have for several years provided several candidates for medical treatments (e.g. Chlorotoxin from Leiurus quinquestriatus (Ehrenberg, 1828) (Buthidae)), but a recent paper suggests that scorpions can contribute with more than their venom.

In a recent article, Atkinson and co-workers present the discovery of antibiotic-producing bacteria in tissue samples from the giant sand scorpion, Smeringurus mesaensis (Stahnke, 1957) (Vaejovidae). It is important to note that this is results from laboratory studies and more research is necessary before the antibiotic effect can be confirmed for humans. But the study opens up the exciting possibility that scorpion tissues can provide a new source of antimicrobial molecules in the war against antibiotic resistance. 

Abstract:
Antibiotic resistance is a global health crisis. Our current arsenal of antibiotics—drugs meant to kill bacteria and stop their population growth—is becoming less effective at treating bacterial infections as resistant bacteria emerge, fueling the dire need to discover new antibiotics. Most antibiotics in use today have been discovered from bacteria. To increase the chances of finding potentially novel antibiotic molecules, we studied the relatively unexplored microbial environment of scorpion tissues, using the giant sand scorpion, Smeringurus mesaensis (Stahnke, 1957). Bacterial symbionts were isolated and cultured from the mesosoma and metasoma, and isolates were tested in a functional assay for production of antibiotics. Under the culture conditions utilized, most scorpion-derived bacteria were from the phyla of Firmicutes, Proteobacteria and Actinobacteria. Fifty five percent of the clonal isolates tested produced antibiotics, with most being Bacillus species. None of the bacterial conditioned media were cytotoxic to mammalian cells. This study suggests scorpion tissues may provide a rich source of antimicrobial molecules to help combat the antibiotic resistance crisis.

Reference:
Atkinson L, Shimwell C, Lucin KM, Graham MR, Murdoch B. Antibiotic-producing bacteria isolated from the giant sand scorpion, Smeringurus mesaensis (Scorpiones: Vaejovidae). The Journal of Arachnology. 2024;52(2):116-26. [Subscription required for full text]

Thanks to Matt Simon for informing me about this article!