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Experimental evaluation of scorpion venom as an anticancer agent

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Title Experimental evaluation of
scorpion venom as an
anticancer agent
 
Creator Das Gupta, Shubho
 
Subject Drug Development/Diagnostics & Biotechnology
 
Description It is the inherent nature of humans to depend upon flora and fauna to find
cures against various ailments. This dependence has given rise to different traditional
medicinal practices throughout the world. Although plants were the prime targets for
explorations for curatives, however animals were not far behind. Various body parts
of the animals were used in the preparations of natural medicines. This practice has
given rise to a distinct branch of medicine called zootherapy. In ancient times,
zootherapists mainly depended on whole body preparations of animals, metabolic
products (corporal secretions and excreta) or non-animal materials (nests and
cocoons). Out of these resources, seven major materials gained prominence for drug
preparations. These are honey, wax, adder, beaver testicles, musk oil, coral, and
ambergris (Lev, 2003). A more detailed insight would reveal a diverse world of
zootherapy. Alexiades (unpublished data) recorded the use of 50 local animals for
traditional drug preparations by the Ese Eja people of Peru. Smashed ants
(Pseudomyrmex sp.) are used by locals of Latin America to cure toothache. Blood
obtained from black caiman (Melanosuchus niger) were used to treat epilepsy and
stroke. In Sudan, honey is used in curing hepatic and gastrointestinal disorders, gastric
ulcers and wound healing. Over 500 species of insects, mites and spiders are used in
to treat complicated diseases in Chattisgarh (Oudhia, 1995). Recent scientific
advances have enlightened the modern world about the medicinal power of
zootherapy and provided a sound scientific basis of these ancient therapeutic practices
that was erstwhile shrouded in an aura of mystery and superstition. The surge in
research into medicines from animals has led to the recognition of 252 essential
chemicals by the World Health Organization. 8.7% of these are directly or indirectly
obtained from animals (Marques, 1997). Out of the 150 prescription drugs used in the
USA, 27 are of animal origin (World Resource Institute, 2000).
Besides these common sources, venoms from venomous animals were also
explored as potential targets for curative discoveries. Venoms are secretory
substances released from venomous animals and are used in self-defense and prey
capture. According to the people of Sierra Madre, ''the more poisonous the animal, the
more potent its antipoison'' (Werner, 1970). Venoms from bees, snakes and scorpions
were used in the traditional medicinal practices of various countries from times
immemorial. Scorpion venom had been used in ancient medicines of China to cure
apoplexy, mumps and tetanus. In India, whole-scorpion soaked oil is used in Eastern
part of Indian to treat arthritic pain. In Cuba, scorpion venom finds use in treating
primary brain tumors.
Scorpions are terrestrial invertebrates that belong to the phylum Arthropoda.
The first scorpions appeared on earth about 425-450 million years ago and were true
aquatic forms. However due to acute scarcities of food, aquatic scorpions were forced
to find new dwelling places on land. Accordingly, morphological and physiological
transformations took place and scorpion fossils with earliest form of air breathing
book lungs were excavated from the 325 million years old Carboniferous deposits of
Europe and North America. After acquiring successful terrestrial adaptations, the
scorpions started to colonize the yet unoccupied territories on earth. The present day
geographical distribution pattern of scorpions clearly depict a bias for their tropical
dwelling. Although there are more than a thousand different species of scorpions,
however only a few of them hold the disrepute of being the lethal varieties. Although
Africa and Asia serves as home to most of the lethal species, several of them also
inhabit Greece, Italy, and Southern France. Of the African species, Androctonus
australis has been reported to be the most dangerous species, which solely account for
the 80% of envenomation and 95% of all scoepion related deaths. Androctonus
hoggarensis and Leiurus quinquestriatus are the other 2 notorious scorpions from
Africa, which come only a close second to the Androctonus australis in envenomation
related deaths. In South America, Tityus serrulatus and Centruroides sp. are
responsible for most deaths due to envenomation. The Middle East Asian varieties of
lethal scorpions are represented by Androctonus crassicauda and Leiurus
quinquestriatus. Buthus martensii is the venomous variety of China, while in India,
Buthus tamulus, Heterometrus bengalensis and Heterometrus swammerdami are the
most toxic species. The later is reported to be the largest scorpion in the world. The
notoriousness of scorpions is solely because of its venom, which lies stored in the
venom gland situated at the extreme end of the telson. The venom gland is a paired
bulbous structure, which opens exteriorly through a narrow tube. The tube in turn is
located in a sting, which is designed for delivering the venom at the subcutaneous
layer of the subject. Prior to the secretion of the whitish and viscous venom, scorpion
secretes a transparent prevenom. The basic purpose of the prevenom secretion is to
reduce the loss of actual venom, which is richer in protein toxins. Prevenom is loaded
with higher K+ content and is mainly used to stun the enemy, induce severe pain and
paralyze the inflicted subject. However actual venom has higher protein content.
Besides protein toxins, venom contains 5-hydroxytryptamine. Majority of scorpion
venom protein toxins are low molecular weight proteins or peptides. Since scorpions
feed on small insects and the venom is specifically directed towards paralyzing their
prey, hence the venom is loaded with channel blocking proteins. Besides paralyzing
their prey, scorpion venom can also produce severe toxic effects in higher animals by
blocking nerve impulse conduction as well. Functionally the toxins can be broadly
classified into Na+ channel, K+ blocking, Ca2+ blocking and Cl- blocking proteins.
Chlorotoxin, a Cl- channel blocking protein purified from the venom of the Israeli
yellow scorpion Leiurus quinquestriatus shows potentials to bind with primary brain
tumors. It has also showed its efficacy in targeting malignant glioma cells and
destroying them. However experiments with normal cells have revealed that
chlorotoxin excludes them for binding preferences. Chlorotoxin binds to the Clchannels
and can thus prevent water loss in the glioma cells. The water loss prevents
the shrinkage of glioma and thereby diminishes their chances of metastasis. Recent
insights have shown that the target molecule of chlorotoxin is the matrix
metalloproteinases-2 (Deshane et al, 2003). Normal brain cells however do not
secrete matrix metalloproteinases. Other than binding to glioma cells, chlorotoxin also
binds to a host of other tissues, which show signs of precancerous modifications
(Lyons et al, 2002).
Among the Indian varieties of scorpions, the Indian black scorpion
(Heterometrus bengalensis Koch) is highly prevalent in the eastern part of India
(Tikader and Bastawade, 1983). As the name suggests, this species of Scorpionida is
abundant in West Bengal and contributes to the most number of scorpion
envenomation related deaths. Very few works have been done on the properties of
Heterometrus bengalensis venom. Lahiri and Nag Chowdhury, 1982 demonstrated
that crude venom induced spontaneous contraction in smooth muscle preparations.
Presence of phospholipase activity in a fraction, isolated from the crude venom was
shown by Kar et al, 1986. Dasgupta et al, 1990 isolated a toxic fraction from the
venom of the Indian black scorpion by CM-cellulose ion exchange chromatography.
However no work has been done till date on the cytotoxic and anticancer properties of
the Heterometrus bengalensis venom. This present study aims at investigating the
cytotoxicity profiles of the venom and the identification of the active fraction(s)
responsible for the said activity. It is expected that the study might put light on the
probable mechanism of action of the anticancer fraction, purified from the crude
Heterometrus bengalensis venom.
 
Date 2011
 
Type Thesis
NonPeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/507/1/ethesis_Shubho_Das_Gupta.pdf
Das Gupta, Shubho (2011) Experimental evaluation of scorpion venom as an anticancer agent. PhD thesis, Jadavpur University.
 
Relation http://www.eprints.iicb.res.in/507/