Experimental evaluation of scorpion venom as an anticancer agent

Das Gupta, Shubho (2011) Experimental evaluation of scorpion venom as an anticancer agent. PhD thesis, Jadavpur University.


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    Gomes, Aparna


    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 Alexiades (unpublished data) recorded the use of 50 local animals for traditional drug preparations by the Ese Eja people of Peru.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.

    Item Type: Thesis (PhD)
    URI: http://www.eprints.iicb.res.in/id/eprint/507
    Subjects: Drug Development/Diagnostics & Biotechnology
    Divisions: UNSPECIFIED
    Depositing User: Mr N C Ghosh
    Date Deposited: 02 Nov 2011 17:12
    Last Modified: 02 Nov 2011 17:12

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