Volume 5, Issue 4, April 2015, Pages 275–276
Document heading
Applications of snake venoms in treatment of cancer
- Open Access funded by Hainan Medical University
- Under a Creative Commons license
Open Access
ABSTRACT
Snake
venoms are folk medicines used since ages. The components of snake
venoms have high specific affinity and actions on cells and cell
components. Also snake venoms are largely cytotoxic to tumor cells than
normal cells. In addition to these, they have several therapeutic
actions that make them an attractive option in the management of cancer.
The advent of modern technologies has greatly helped in extracting and
identifying new components of therapeutic interests in short time. The
article highlights the importance of snake venoms in the management of
cancer, so as to motivate curious researchers to devote their skills in
this fascinating area. This in turn may bring hope, smile and relief to
several cancer patients in future.
Keywords
- Snake venoms;
- Cancer;
- Management;
- Biotoxins
1. Introduction
Snake
venoms have the highest toxicity potential that makes them an
attractive option in the development of anticancer agents. Evolution of
modern high throughput screening systems has helped to recognize and
extract new therapeutic substances from biotoxins such as venoms of
several snakes that show promising potential to combat cancer. Growing
understanding of molecular mechanism is also contributing in this
direction[1].
Snake
venom is a complex mixture of enzymes, peptides, carbohydrates,
minerals and proteins of low molecular mass with specific chemical and
biological activities[2 and 3].
Components of snake venoms can be used in the treatment of cancer,
arthritis, thrombosis, multiple sclerosis, pain, neuromuscular
disorders, blood and cardiovascular disorders, infections and
inflammatory diseases[1, 2 and 3].
Snake venom contains cytotoxins, cardiotoxins, hemotoxins, neurotoxins,
nerve growth factor, inorganic cations like zinc, calcium, potassium,
sodium and magnesium, etc. Phospholipase A2, ancrod,
cobra venom factor, peptides, cytotoxins CT1, CT2 and CT3, crotoxin,
L-amino acid oxidases (LAAOs), lectins, metalloproteinases,
disintegrins, serinoproteases, hyaluronidase, cholinesterases, salmosin,
cathelicidin-BF, aggretin, obtustatin, rhodostomin, albolabrin,
colombistatin, saxatilin and lebecetin are some of the components
isolated from various snake venoms, which show promising applications in
management of various human cancers. Several researches have been
conducted on actions of snake venoms on tumor cell cultures and some of
them are in phase I and phase II clinical trials[ 3, 4, 5 and 6].
Disintegrins, like contortrostatin isolated from Agkistrodon contortrix
venom prevents cells from adhering together and inhibits their
interaction with surrounding tissue, resulting in decreased cell
motility and invasiveness[ 1].
Cytotoxic effect of snake venom has potential to directly destroy tumor
cells. Fibrin deposition around tumor could form a protective barrier,
but also prevent tumor progression. Also fibrin deposits formed by
metastatic tumor cells may help disseminating these tumor cells. Snake
venom containing ancrod, a polypeptide can produce defibrination and
decrease spread of some tumors[ 1, 3 and 4].
C-type lectins inhibit integrin-dependent proliferation, migration,
invasion, and angiogenesis. C-type lectins have been isolated from Macrovipera lebetina snake venom. Secreted phospholipases A2 (sPLA2) isolated from Cerastes cerastes and Macrovipera lebetina have promising antitumor and antiangiogenic properties since they act specifically on integrins α5β1 andαβ[ 7]. Also sPLA2 from Daboia russelii siamensis
venom shows cytotoxic effect and inhibits cell migration in human skin
melanoma cells. It also reduces tumor lung colonization of B16F10
melanoma cells in BALB/c mice. sPLA2 has anticoagulant
properties which may prevent recurrent thrombosis, which is the second
most common cause of death in cancer patients[ 8].
2. Snake venom components
Snake
venom containing cystatin decreases tumor invasion and metastasis.
Snake venom components can be specifically directed to cancer cells by
combining the components with nanoparticles[5].
Cobra venom factor is an important factor for the synthesis of
immunoconjugates, which are more specific towards carcinoma cells[3].
Cobra venom in very minute doses has powerful analgesic activity than
morphine and can reduce intractable pain associated with cancer[1 and 2].
The enzyme LAAOs isolated from snake venoms induce apoptosis,
alterations in cell cycle processes and cytotoxicity and have promising
potentials in development of new antitumor agents[9 and 10].
Production of hydrogen peroxide during enzymatic reaction, caspases
activation and interaction of LAAOs with membrane receptors are some of
the possible mechanisms behind the actions of snake venom LAAOs[10].
Snake
venom components basically inhibit cell proliferation and promote cell
death. Mechanisms of action include: increasing calcium ion influx,
inducing cytochrome C release, increasing or decreasing the expression
of proteins that control cell cycle, inflicting cell membrane damage,
anti-platelet action preventing fibrin formation, preventing thrombin
induced metastasis, inducing cancer cell apoptosis thereby controlling
tumor size, direct toxicity and free radical generation, inhibiting
nucleic acid synthesis thereby suppressing cell proliferation,
decreasing the expression and activity of matrix metalloproteinases,
inhibiting integrins thereby preventing migration and invasion of cancer
cells, and antiangiogenesis. Cytotoxicity of snake venoms is related to
alterations in cellular metabolism with a major effect on tumor cells
when compared with normal cells[3, 4 and 5].
3. Conclusions
Venoms of Bothrops newweidii, Indian cobra Naja Naja, Naja nigricollis, Naja naja atra, Bothrops Leucurus, Opiophagus Hannah, Bothrops jararacussu, Naja Kaouthia, Okinawa Habu, Lapemis curtus, Daboia
russelli russelli, Walterinessia aegyptia, Crotalus durissus
terrificus, Agkistrodon acutus, Macrovipera lebentina, Bungarus
multicinctus, Bungarus fasciatus, Laticauda semifasciata and Agkistrodon
rhodostoma are of potential use in research directed towards management of cancer[ 1, 2, 3, 4, 5 and 6].
Tagging gold nanoparticles with snake venom components has been found to increase their uptake by tumor cells[11].
Also silica nanoparticles tagged with snake venom components are
observed to act specifically on tumor cells without affecting normal
cells[12].
Novel snake venom delivery system with clinical applications to
suppress tumors such as intravenous liposomal delivery, recombinant
adenovirus carrying snake venom cystatin gene has been described in the
literature[6].
Innovative research is required to discover novel, effective
therapeutic anticancer agents from snake venoms in oral cancer patients.
This promising area of research may bring hope, smile, comfort and cure
to these group of cancer patients.
Conflict of interest statement
We declare that we have no conflict of interest.
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