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In this article we will discuss about the applications of lectin in field of genetics.
Lectins are proteins, or glycoproteins, that agglutinate erythrocytes of some or all blood groups in vitro. They are an important group of bioactive proteins and glycoproteins found in most organisms, including plants, vertebrates, invertebrates, bacteria and viruses, and have several important applications to the fields of health food and medical biotechnology.
Lectins are used as tools in the fields of biochemistry, cell biology and immunology, as well as for diagnostic and therapeutic purposes in cancer research.
Lectin aggregation can be employed on a large-scale basis for the commercial production of biologically active proteins. Lectins have been used in glycoprotein purification, oligosaccharide analysis, as well as in cell- selection processes. Lectins can bind reversibly with free – sugars or with sugar residues of polysaccharides, glycoproteins or glycolipids.
There has been increasing demand for novel diagnostic and medical cancer therapies that utilise non-traditional sources. Epidemiological studies indicate that the consumption of a plant-based diet is strongly associated with a reduced risk of developing several types of cancer.
Plants contain numerous phytochemicals that can alter cancer-associated biochemical pathways. One such group being intensively examined for its role in cancer chemoprevention is lectins. Lectins are currently being considered for use as cancer therapeutic agents. Lectins were reported to bind preferentially to cancer cell membranes, or their receptors, causing cytotoxicity, apoptosis and/or tumor growth inhibition.
Lectins were thought to become internalised into cells, and some lectins were claimed to cause cancer cell agglutination and/or aggregation. Present in common foods, some lectins resist acid and/or enzymatic digestion and also were reported to enter the bloodstream in an intact, and biologically active, form. Lectins possess a spectrum of beneficial, as well as harmful, effects both in vitro and in vivo.
Ingestion of lectins also sequesters the available body pool of polyamines, thereby claimed to thwart cancer cell growth. They have also been reported to affect the immune system by altering the production of various interleukins, or by activating certain protein kinases.
Lectins were also reported to bind to ribosomes and thus inhibit protein synthesis. Lectins may also modify the cell cycle by inducing non-apoptotic G1-phase accumulation mechanisms, G2/M phase cell cycle arrest, and apoptosis, and might activate the caspase cascade. Lectins were also reported to down-regulate telomerase activity and inhibit angiogenesis.
Lectins could inhibit cell adhesion, proliferation, colony formation and hemagglutination, and were reported to have cytotoxic effects on human tumor cells. Lectins could function as surface markers for tumor cell recognition, cell adhesion, and signal transduction across the membrane, mitogenic cytotoxicity and apoptosis.
Also, lectins were reported to modulate the growth, proliferation and apoptosis of premalignant and malignant cells both in vitro and in vivo. Most of these effects are thought to be mediated by specific cell surface receptors. For many years, lectins have been considered toxic substances to both cells and animals, mainly because of the observed agglutination of erythrocytes and other cells in vitro.
On the other hand, it has also been reported that lectins have an inhibitory effect on the growth of tumors. Their potential for clinical applications has been investigated only in recent years. Lectins are now being considered for use both in the diagnostics and therapeutics of cancers.
Thus, lectins are quite versatile biomarkers and have been utilised in a variety of studies involving histochemical, biochemical and functional techniques for cancer cell characterisation. Lectins may also be very useful tools for the identification of cancers and the degree of metastasis, or cancer development stage.
Recently, there has been a tendency to shift lectins use from cancer detection to actual use in combating cancer. The reason for this shift is mainly caused by recent research that indicated the cytotoxic and apoptosis/necrosis-inducing effects of certain lectins, combined with the hypothesis that dietary lectins enter the systemic circulation intact.
One important feature appears to be that lectins stimulate the human immune system. Lectins were thus reported to exhibit antitumor and anticarcinogenic activities that could be of substantial benefit in cancer treatment.
Extracts of Viscum album (mistletoe) are widely used as complementary cancer therapies in Europe. Mistletoe has been used parenterally for more than 80 years as an anticancer agent with strong immuno-modulating action. The quality of life of patients with late-stage pancreatic cancer was reported to be improved on account of exposure to mistletoe lectin.
Immuno-modulation using recombinant ML was reported to influence tumor growth in breast cancer patients. Bladder carcinoma was reported to be significantly reduced, and survival times were reported to be prolonged in mice as the concentration of ML was increased from 3 to 30 ng. ML increased the life span, decreased the tumor growth and decreased hyperplasia of mice and rats with lymphoma and lung cancer.
A lectin purified from mesquite seed was reported to have an anti-proliferative effect on the cervical human tumor (HeLa) cells and on cell adhesion. Interestingly, mesquite lectin modulated the growth, proliferation and apoptosis of HeLa cells, while having no effect on normal cells in vitro. Vicia faba agglutinin (VFA), a lectin from broad beans was reported to aggregate, stimulate the morphological differentiation of, and reduce the malignant phenotype of colon cancer cells.
Wheat germ agglutinin (WGA) proved to be highly toxic to human pancreatic carcinoma cells in vitro. WGA exposure induced chromatin condensation, nuclear fragmentation and DNA release, consistent with apoptosis.
The binding of the snail lectin Helix pomatia agglutinin (HPA), which recognises N-acetylgalactosamine and N- acetylglucosamine sugars, is considered to be a strong predictor of metastasis and unfavourable prognosis in a number of human adenocarcinomas, including breast cancer.
Because of their carbohydrate bio-recognition properties, lectins may also be used as carriers for targeted drug delivery, in a manner similar to liposomes, provided the possible side effects of such treatments could be minimised.
It has been observed that mucosal expression of terminal un-substituted galactose is increased in colon pre-cancerous conditions and cancer, and that it allows interaction with mitogenic galactose-binding lectins of dietary or microbial origin. Based on this observation, an interesting hypothesis was postulated whereby galactose might be able to prevent cancer by binding and inhibiting such lectins from interacting with colon cancer cells.
D-galactose treatment was reported to be effective in liver lectin blocking to prevent hepatic metastases in colorectal carcinoma patients. Epithelial cancer cells showed an increased cell surface expression of mucin antigens with aberrant O-glycosylation, notably Thomsen- Friedenreich Antigens (TFA).
TFA is a carbohydrate antigen with a proven link to malignancy. Immunoassays could be utilised for antigens such as TFA in order to determine the metastatic potential of breast and colon cancer cells.
Molecular changes in the membrane surface in the case of both stomach and colon cancer cells occur during the progression to carcinogenesis. Carbohydrate patterns displayed on the cellular membrane exterior are molecular signatures with unique biological characteristics related to oncogenesis and metastasis, and could be used to determine the appropriate chemotherapeutic and surgical procedures for each specific cancer.
Lectins have already a demonstrated potential for the treatment, prevention and diagnosis of chronic diseases such as cancer. Further research is, however, required to further elucidate the effects of purified and dietary lectins and their potential for defense against tumors.