Plant origin lectins and its application in treatment of cancer .

1. PRIYADARSHINI INSTITUTE ENGINEERING AND
TECHNOLOGY, NAGPUR
DEPARTMENT OF BIOTECHNOLOGY
BY-
MR.DHIRAJ SANJAY POWAR
Final year ,
Department of Biotechnology
SEMINAR ON –
“Lectins In Cancer Therapy”
Dhirajpowar 1

2. •
OVERVIEW
PRESENT SCENARIO OF CANCER
LECTINS – AN INTRODUCTION
THE STORY OF LECTIN
PROPERTIES
ROLE OF LECTINS
LECTINS IN THERAPEUTICS
FUTURE PROSPECT
SUMMARY AND LIMITATIONS
REFERENCES
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3. Present Scenario Of Cancer
• Cancer is among the leading causes of death worldwide after
cardiovascular disease.
• According to Global Burden of Cancer report 2014 , there
were 1.17 million new cancer cases in India whereas 6,75,000
deaths in 2014.
• In next decades, it will expected to rise of new cases up to 70
% worldwide, due to population aging and growth.
• Cancer treatments are available but those treatments has some
disadvantages.
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4. Lectins-an Introduction
• Lectins are a group of proteins (or glycoproteins ) of non-immune
origin that bind specifically, reversibly and non-covalent to
carbohydrates, particularly the sugar moiety of glyco-conjugates .
• Lectins are tetramer made up
of 4 nearly identical subunits
• They function as both allergens and
hem-agglutinins.
• Nowadays, proteins that can agglutinate
red blood cells with known sugar
specificity are referred to as “lectins”.
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5. Story of Lectin
 Lectins have been known for a century. They were discovered in
castor beans by Stillmark in 1888 at Estonia University and in non-
toxic plants (beans and lentils) in 1907.
 By 1945 Boyd found that some lectins were blood-type specific. He
reported that lima beans will only agglutinate blood type A. Since
that time many lectins have been identified.
 The Name Lectin comes from Latin “legere” means to choose or
select.
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6. Properties of Lectins
• Lectin proteins contain at least one carbohydrate-binding domain.
• Involved in cell Interactions.
• Similar to Antibodies and involved in normal and biological process.
• They are carbohydrate binding proteins that are highly specific for
sugar moieties.
• Induces apoptosis and type-Ⅱ Programed cell death(autophagy) in
cells.
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7. Role Of Lectins
Figure 1: Various role of Lectins 7Dhirajpowar

8. Lectins In Cancer Therapy
• Plant lectins seem to have great potential as anticancer therapeutic agents.
• Glycosylation alteration occur in Cancer cells at different stages .
• Tumor cells express carbohydrates on their cell surface .
• The Lectins shows ability to target multiple cellular components present
on tumor cells .
• The effector Mechanism induced by lectins on cancer cell :
1.cell agglutination / aggregation
2.Apoptosis
3.Autophagy Extraordinary effectiveness!8Dhirajpowar

9. Figure 2: Mechanisms of apoptosis and autophagy induced in tumor cells by
lectins 9Dhirajpowar

10. Results of ML-1against Cancer cell line
Fig. 3 :ML-I-induced release of cytochrome c precedes the loss of DCm and
apoptosis. 10Dhirajpowar

11. In figure 3 :
• A=time-course of mitochondrial cytochrome c release: Jurkat cells were
pretreated with medium or 100 mM zVAD-fmk for 1 h and then either left
untreated or incubated with 10 ng/ml ML- I. After the indicated time, cells were
homogenized, and the S10 fraction depleted of mitochondria was loaded on a
15% SDS-PAGE. The release of cytochrome c into the cytosol was determined
by immunoblotting.
• B=histogram analysis of the ML-I-induced reduction of DCm: cells were
treated with 10 ng/ml ML-I and, after the indicated times, DCm was determined
by staining cells with the potential-sensitive fluorochrome-3, 39-
dihexyloxacarbocyanine iodide.
• C=time-course of ML-I-induced loss of DCm (circles) and onset of apoptosis
(triangles): The percentage of cells with a low DCm and hypo-diploid DNA was
evaluated in a flow cytometer. The dashed lines show the values of untreated
cells, and the closed lines show the values of cells treated for the indicated time
with ML-I.
• D=effect of zVAD-fmk on ML-I-induced loss of DCm: the graph indicates
DCm values that were assessed 24 h after stimulation of cells in the presence
(M) or absence (f) of zVAD-fmk . 11Dhirajpowar

12. Lectins And Its Induced Mechanism On Cancer Cell
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13. Advanced in technology
• Recently, Mistletoe extract containing lectin has been used clinically
at low doses in the treatment of different cancers without serious
side effects.
• It showed positive results on human breast cancer when mixed with
DOX toxin .
• Anti-cancer action of a new recombinant lectin produced from
Acacia species.
The secret of Herbal Medicines
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14. Can Lectins Neutralize HIV?
• Now a days ,lectins are used for the treatment of HIV.
• Lectins with specificity for the terminal alpha-1-3 and alpha-1-6-mannose
terminals on HIV will cause a neutralization of the viral capsid in vitro.
• Galanthus nivalis (snow drop) has been shown to afford cellular protection by
blocking the HIV's ability to bind to cell surfaces.
• Additionally, it may protect cellular surfaces by blocking HIV binding sites
before the virus can attach. This is especially felt to be the case with CD4 cells
as they contain a large number of alpha-1-3 and alpha-1-6-mannose terminals.
• Other lectins such as those from lentil, wheat germ agglutinin and Phaseolis
vulgaris have also shown an effect upon the ability of HIV to bind to cell
surfaces
Aiding AIDS!!!! 14Dhirajpowar

15. Summary
• In summary, the use of lectins obtained from natural plant and
animal sources shows great promise and potential for use in future
cancer therapy. Current research has found strong anti-cancer effects
of many lectins. Both apoptosis and autophagy are important factors
that influence the success of lectin chemotherapy.
• The therapeutic effects of lectins seem to take place at lower
concentrations rather than at the higher ones.
• The new recombinant lectin proteins encourage us to study their
cytotoxicity on cancer cells as anticancer agent.
Anti–bacterial, also Anti–Cancerous
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16. Limitations
• It is Similar to Antibody, so it will cause Blood Clauting-
hemagglutinin.
• Danger when consumed in their raw state, or by persons deficient in
stomach acid, proteolytic enzymes, or Secretory- IgA.
• Food containing high concentration of lectins may be harmful when
it consumed in excess or in improper cooked food such as grains,
pulses, seeds ,beans and potatoes .
Lectin toxicity and the Irony…16Dhirajpowar

17. Future Prospect
 Bacterial Capturing.
 Lectins as Nano-Tool in Drug Delivery .
 Plant lectins as tool in biology and medicine.
 Anti-adhesion therapy of bacterial diseases.
 Animal lectins in cell recognition- Immune stimulants.
 Hormone modulators.
As a Diagnostic Aid…17Dhirajpowar

18. References
1. National Cancer Institute –https://www.cancer.gov/
2. “1990–2013: A systematic analysis for the Global Burden of
Disease Study 2013”, Volume -385, No. 9963 , p117–171, 10
January 2015.
3. Roberto A. Ferriz-Martinez ,Iovanna C., “Torres-Arteaga,2010,The
role of Plant Lectins in Cancer Treatment”, New Approaches in the
Treatment of Cancer ,ISBN978-1-61728-3048.
4. Tammy Yau , Xiuli Dan , Charlene Cheuk Wing Ng and Tzi Bun
Ng , 26 February 2015, “Lectins with Potential for Anti-Cancer
Therapy ”, ISSN 1420-3049.
5. Heike Bantel,Ingo H. Engels, Wolfgang Voelter, Klaus Schulze-
Osthoff, and Sebastian Wesselborg , 1 May , 1999,“Mistletoe Lectin
Activates Caspase-8/FLICE Independently of Death Receptor
Signaling and Enhances Anticancer Drug-induced Apoptosis” ,
CANCER RESEARCH 59, 2083–2090.
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19. Thank You
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