Natural product-derived  therapy for enhancing anti-cancer immunity: Nimbolide, isolated from Neem (Azadirachta Indica), decreases the level of LATS1/2 (large tumor suppressor 1 and 2), increases immunogenicity of tumors, enhances anti-tumor immune responses, and inhibits tumor growth via down regulation of its target gene, 24/December/2017, 12.35 am

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Introduction: What they say: 

A study from the Department of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA shows that “The Hippo Pathway Kinases LATS1/2 Suppress Cancer Immunity.” This study was published, in the 1 December 2016 issue of the journal “Cell” [the number 1 journal in General Biology with an I.F of 28.710], by Prof. Guan KL, Moroishi T, and others.


What we say: 

On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Natural product-derived  therapy for enhancing anti-cancer immunity: Nimbolide, isolated from Neem (Azadirachta Indica), decreases the level of LATS1/2 (large tumor suppressor 1 and 2), increases immunogenicity of tumors, enhances anti-tumor immune responses, and inhibits tumor growth via down regulation of its target gene


From Significance of the study to Public health relevance:

Given that: (i) each year nearly 14 million people are diagnosed with cancer globally, and little more than half of them will die; (ii) cancer deaths globally are expected to be doubled by 2030; (iii) cancer treatment causes the highest economic loss compared to all the known causes of death worldwide, there is an urgent need to find: (i) a way to prevent an individual from being susceptible to cancer by strengthening his/her own immune system; (ii) a cheaper alternative to the existing expensive anticancer drugs; (ii) a side-effect-free natural product-based drug; and (iii) a way to effectively treat and prevent metastatic progression and relapse of cancers.

price-300


What we infer from what they say:

Prof. Guan’s research team has recently shown that deletion of Lats1/2 in tumor cells: (1) augments  cytotoxic T cells activity; (2) enhances antibody production by B-cells; (3) enhances anti-tumor immunity by stimulating TLRs-MYDD/TRIF-IFN-I pathway; (4) enhances YAP (Yes-associated protein) activity; and (5) augments tumor vaccine efficacy, suggesting that inhibition of LATS1/2 expression in cancer cells may augment immune system’s ability to prevent tumor growth.


From research findings to therapeutic opportunity : 

This study suggests a natural product-derived therapy for augmenting anti-cancer immunity.

[easy_payment currency=”USD”]

Nimbolideby decreasing the expression of its target genes, it may decrease the expression of LATS1/2. Thereby, it may: (i) enhance Cytotoxic T-cell activity and antibody production by B-cells; (ii) enhance anti-tumor immunity via Interferon-I pathway (TLRs-MYDD/TRIF); (iii) increase the expression of transcriptional coactivator YAP, possibly, its target gene p53 homologue TAp73; (iv)  increase tumor vaccine efficacy; and (v) promote tumor regression (fig.1).

Figure 1 . Mechanistic insights into how Nimbolide functions as an anti-cancer agent. Andrographolide suppresses the expression of Lats1/2 and activates Interferon-I pathway to promote tumor regression

Figure 2. The chemical structure of Nimbolide.

Thus, pharmacological formulations encompassing “Nimbolide or its analogues, either alone or in combination with other anticancer drugs(fig.1) may be used to strengthen cancer patients immune system to prevent tumor growth and cancer progression.


Details of the Research findings:  

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

Amount: $300#

Undisclosed mechanistic information: How does Nimbolide  decrease the expression of LATS1/2 to inhibit tumor growth?

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References: 

Web: http://genomediscovery.org or http://newbioideas.com

Citation: Boominathan, L., Natural product-derived  therapy for enhancing anti-cancer immunity: Nimbolide, isolated from Neem (Azadirachta Indica), decreases the level of LATS1/2 (large tumor suppressor 1 and 2), increases immunogenicity of tumors, enhances anti-tumor immune responses, and inhibits tumor growth via down regulation of its target gene, 24/December/2017, 12.33 am, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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