Natural product-derived PD-1 pathway blockade for Human cancer therapy: Alantolactone, present in Inula helenium, L. Inula japonica, Aucklandia lappa, Inula racemosa, and Radix inulae, decreases the activity of Glycogen synthase kinase-3β, increases transcription factor T-bet expression, decreases the abundance of co-inhibitory receptor PD-1 on the cell surface of Cytotoxic-T-cells, increases cytotoxic T lymphocyte function and augments anti-tumor activity, via up-regulation of its target gene, 19/January/2017, 11.58 pm

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Introduction:What they say

A recent study from Cell Signalling Section, Division of Immunology, Department of Pathology, Tennis Court Road, University of Cambridge, Cambridge CB2 1QP, UK shows that “Glycogen Synthase Kinase 3 Inactivation Drives T-bet-Mediated Downregulation of Co-receptor PD-1 to Enhance CD8(+) Cytolytic T Cell Responses.” This study was published in the 16 February 2016 issue of Immunity (one of the best journals in Immunology with an impact factor of 20+) by Prof Rudd CE, Taylor A and others.


What we say

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On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Natural product-derived PD-1 pathway blockade for Human cancer therapy:  Alantolactone, present in Inula helenium, L. Inula japonica, Aucklandia lappa, Inula racemosa, and Radix inulae, decreases the activity of Glycogen synthase kinase-3β, increases transcription factor T-bet expression, decreases the abundance of co-inhibitory receptor PD-1 on the cell surface of Cytotoxic-T-cells, increases cytotoxic T lymphocyte function and augments anti-tumor activity, via up-regulation of its target gene


What is known?

It has recently been shown that blocking PD-1 with antibodies one could make tumors shrink. This work, relating to Cancer immunotherapy, has been chosen as Science’s breakthrough of the year.


Research Findings

This study suggests a natural product-based Human cancer therapy.  Alantolactone, by increasing the expression of its target gene, it may suppress the expression of Glycogen synthase kinase 3-β (figures 1-3).

Inula helenium, க்கான பட முடிவு

Figure 1. Alantolactone, found in Inula helenium  among others, as indicated below, augments anti-tumor immunity via down regulation of PD-1

Inula japonica க்கான பட முடிவு

Fig 2. Inula japonica

 க்கான பட முடிவு

Fig 3. Alantolactone boosts anti-tumor immunity. Alantolactone, isolated from Inula helenium, L. Inula japonica, Aucklandia lappa, Inula racemosa, and Radix inulae, increases T-bet expression, inhibits PD-1 expression, and augments anti-tumor immunity

Thereby, it may: (a) increase transcription factor T-bet expression; (b) inhibit co-inhibitory receptor PD-1 expression;  (c) increase CD8(+) cytotoxic T lymphocyte function; (d) augment anti-tumor activity; & (e) inhibit metastatic cancer progression (fig 3).


Therapeutic opportunity

Thus, pharmacological formulations encompassing Alantolactone or its analogues may be used to inhibit the progression of tumors.


Details of the research findings:

Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.

Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/

Amount: $50

Undisclosed information: How does   Alantolactone suppress the expression of PD-1 to promote anti-tumor immunity?

# Research cooperation

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References:

Citation: Boominathan, L., Natural product-derived PD-1 pathway blockade for Human cancer therapy:  Alantolactone, present in Inula helenium, L. Inula japonica, Aucklandia lappa, Inula racemosa, and Radix inulae, decreases the activity of Glycogen synthase kinase-3β, increases transcription factor T-bet expression, decreases the abundance of co-inhibitory receptor PD-1 on the cell surface of Cytotoxic-T-cells, increases cytotoxic T lymphocyte function and augments anti-tumor activity, via up-regulation of its target gene, 19/January/2017, 11.58 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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