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CHLOROTOXIN
ASHLEY SANCHEZ
ANDREA POHL
VANESSA MICHEL
Toxins
 What is a toxin?

A toxin is a poisonous
substance that is a specific
product of the metabolic
activities of a living
organism. It is usually
very unstable, notably
toxic when introduced
into the tissues, and
typically capable of
inducing antibody
formation.
 What is a neurotoxin?

A neurotoxin is a
substance that damages,
destroys, or impairs the
functioning of nerve
tissue.
What is chlorotoxin?
 "Chlorotoxin (CTX), a 4-kD peptide purified from Leiurus
quinquestriatus scorpion, is a highly specific marker for
glioma cells in biopsy tissues that can target tumors in
animal models.”
 Put more simply: "Chlorotoxin is a 36-amino
acid peptide found in the venom of the deathstalker
scorpion (Leiurus quinquestriatus) which blocks smallconductance chloride channels."
Why we chose chlorotoxin?
 We found the venom, Chlorotoxin, to be very
interesting because of its possible impact on cancer
treatment, especially brain cancer, which has faced
many obstacles in finding safe, effective treatment.
The source of the toxin is from the venom of a
scorpion, which further emphasizes that toxins can
be harmful but also potentially beneficial
depending on the dose.
Where does chlorotoxin come from?
 Chlorotoxin can be purified from crude leiurus,
which belongs to scorpion toxin super family.
Leiurus quinquestriatus
 Habitat
 Deathstalkers are found in arid and hyper-arid regions of
North Africa and the Middle East. They generally reside under
rocks or in abandoned burrows of other animals. They also
create their own burrows about 20 cm below rocks.
 Geographic range
 "Deathstalkers, Leiurus quinquestriatus, are native to the
Oriental, Palearctic, and Palearctic regions.”
 Behaviors
 Deathstalkers are nocturnal, which helps manage temperature
and water balance, important functions for survival in dry
habitats. Many species of scorpions dig burrows in the soil.
They have flat bodies, allowing them to hide in small cracks,
under rocks and under bark
Deathstalker scorpion
venom contains
chlorotoxin which can
have serious effects on
the individual who is
stung. The shape of
chlorotoxin is very
important. It is the
perfect shape to fit in
Chloride ion channels,
and irreversibly block
them. By doing this, it
prevents the muscle cell
from receiving an influx
of chloride ions which it
usually recieves for
normal muscle
functioning. This results
in muscle contraction,
and possibly paralysis.
Mechanism
What to do if stung…
 It is vital to receive medical attention as soon as
possible after a sting.

Although painful, few people die but those with allergies or
heart issues are at greater risk of death if stung.
 It is important to apply ice in the area of the sting.
 Treatment includes the administration of anti-
venom, pain medication and some antihistamines.
 Symptoms will vary among patients.

Some experience a wide array of symptoms while others
experience mild symptoms.
Anti-venom Treatment
 Although the Deathstalker Scorpion is regarded as one of
the most toxic scorpions, stings are not usually fatal.
 There is an anti-venom which is used for the treatment of
Deathstalker stings. It has no effect on Chlorotoxin proteins
that are already blocking Chloride channels, but rather
works by changing the shape of Chlorotoxin so it cannot
bind and block Chloride channels. Preventing the problem
from getting worse.
Ancient Uses of Scorpion Venom
 In imperial China, scorpion venom was used to treat
ailments such as mumps and tetanus
 In India, whole scorpions were dipped in mustard oil
and rubbed on arthritic joints to treat pain
Chlorotoxin and Gliomas
 In 1996, Ullrich and Sontheimer found that
Chlorotoxin was effective in blocking chloride
channels in glial cells by as much as 80%.
 They also found that cell proliferation decreased as
chloride channels were blocked, suggesting a link
between the chloride channels and growth control.
 Soroceanu et al (1998) found the toxin probably
binds to glioma-specific chloride ion channels or
another receptor that affects the channel’s activity.
Chlorotoxin and Other Cancer Cells
 In 2002, Lyons et al found that Chlorotoxin can bind to a
number of tumor cells, even though they have different
membrane composition.
 They stained tissues from 48 various peripheral tumors of
neuroectodermal origin, 63 from gliomas and 151 comparison
tissue samples with a chlorotoxin derivative.

Comparison tissue samples were healthy tissues from the same organ.
 Over 95% of the glioma cells showed specific binding of the
chlorotoxin derivative.
 The chlorotoxin derivative bound well to other brain tumor
cells, as well as melanoma, carcinoma and
pheochromacytoma tissues.
 Healthy tissues were mostly untouched by the toxin.
Medical Possibilities for Chlorotoxin
 Dr. Steven Rosenfeld is conducting a series of trials
at the NewYork-Presbyterian using radioactive and
non-radioactive chlorotoxin to inhibit angiogenesis,
or the tumor’s ability to grow blood vessels.



The first clinical, which has been completed, saw radioactive
chlorotoxin delivered locally to the brain tumor site via a thin
catheter.
In the second trial, which is currently underway, patients are
receiving a non-radioactive chlorotoxin delivered
intravenously.
The third trial will see patients receiving radioactive
chlorotoxin intravenously.
Medical Possibilities for Chlorotoxin
 Tumor Paint
 Dr. Jim Olson is working on developing a chlorotoxin
biconjugate that will stain cancer cells so surgeons can
more easily remove the tumor during surgery.

Tumor Paint attaches to cancerous cells and illuminates them so surgeons
can distinguish them from healthy cells.
Chlorotoxin (CTX) is an
up and coming
important toxin in the
development of gliomaspecific nanoparticles.
Chloride channels are
CTX receptors, and
matrix
metalloproteinase-2
(MMP-2) has been
identified as a second
CTX receptor. MMPs are
a family of enzymes that
are responsible for
specifically cleaving
components of the
extracellular matrix.
MMP-2 is upregulated in
gliomas and other
related cancers.
CTX Nanoparticles
Medical Possibilities for Chlorotoxin
 Gene Therapy
 In a study by Kievit et al, researchers developed nanoparticles
that had DNA encoding green fluorescent expression and
attached them to chlorotoxin.
 They studied gene delivery to glioma cells in mice.
 There was enhanced uptake of these particles in cancer cells, as
evidenced by higher gene expression.
The DNA-attached
chlorotoxin saw much
higher localized expression
of the green fluorescent
protein in tumor cells
Medical Possibilities for Chlorotoxin
 The research on this toxin has shown the great
potential it has to further cancer treatment.
 Its ability to affect cancer cells without harming
healthy cells makes it a safe alternative to current
treatments such as chemotherapy.
 It can potentially help inhibit growth of tumors,
deliver genes that can act on cancer cells, and light
up tumors, helping surgeons remove whole tumors
while leaving healthy tissue unharmed.
The Good
 Chlorotoxin was originally isolated from venom of
deathstalkers and is now being used in cancer research and
treatment.
 More research is being done in regards to the possible use of
other components of deathstalker’s venom in the treatment of
diabetes because as channels on which the neurotoxins act
have been linked to the regulation of insulin.

However, such research is still in its early stages.
 Scorpions are also good bio-indicators, as they are K-selected
equilibrium species that comprise a major group of predatory
arthropods in arid ecosystems.
 Their disappearance often indicates habitat degradation and
there are programs to conserve terrestrial invertebrates that
often target scorpions.
The Bad
 Deathstalker scorpions use venom as a defense
mechanism. As a result, this can have very painful
(and sometimes deadly) consequences for the
individual stung.
Why you should care
 Chlorotoxin has exhibited itself to be a useful peptide
in the research and treatment of different cancers
and medical issues. This toxin has a major impact on
the medical world, as well as in the lives of those
with cancer.
 The main take-home message that is further
exhibited by chlorotoxin is that toxins can be
harmful AND helpful.
Works Cited
 Fu, y., An, N., Li, K., Zheng, Y., Liang, A. (2011). Chlorotoxin-conjugated

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nanoparticles as potential glioma-targeted drugs. Journal of NeuroOncology. 107:457-462.
Kievit, F. M., Veiseh, O., Fang, C., Bhattarai, N., Lee, D., Ellenbogen, R. -G.,
and Zhang, M. (2010). Chlorotoxin labeled magnetic nanovectors for
targeted gene delivery to glioma. ACS Nano, 4.8: 4587-94.
Lyons, S. A., O'Neal, J. and Sontheimer, H. (2002), Chlorotoxin, a scorpionderived peptide, specifically binds to gliomas and tumors of
neuroectodermal origin. Glia, 39: 162–173.
Soroceanu, L., Gillespie, Y., Khazaeli, M. B., and Sontheimer, H. (1998). Use
of chlorotoxin for targeting of primary brain tumors. Cancer Research, 1.58:
4871-9.
Ullrich, N. and Sontheimer, H. (1996). Biophysical and pharmacological
characterization in human astrocytoma cells. American Journal of
Physiology, 270.5: 1511-21.
Works Cited
 http://www.merriam-webster.com/dictionary/toxin
 http://medical-dictionary.thefreedictionary.com/neurotoxin
 http://www.ncbi.nlm.nih.gov/pubmed/12112367
 http://en.wikipedia.org/wiki/Chlorotoxin
 http://www.alomone.com/p/chlorotoxin/rtc-450/682
 http://animaldiversity.org/accounts/Leiurus_quinquestriatus/
 http://www.scorpionworlds.com/deathstalker-scorpion/
 http://askabiologist.asu.edu/venom/
 http://www.wired.com/2014/06/scorpion-venom/
 http://nyp.org/deathstalkerscorpion/clinical_trial.html