Natural product-derived therapy for enhancing anti-cancer immunity: Celastrol, isoalted from Thunder God Vine/Tripterygium Wilfordii, 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, 4/February/2017, 11.02 pm

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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: Celastrol, isolated from Thunder God Vine/Tripterygium Wilfordii, 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 gen


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.


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 will 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. Celastrol is known to function as an anticancer agent. However, its detailed mechanism of action is yet to emerge.

price-300[easy_payment currency=”USD”]

Celastrol, by 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 (figs.1-4).

Celastrol inhibits LATS1 expression

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

Thus, pharmacological formulations encompassing Celastrol 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: $100#

Undisclosed mechanistic information: How does Celastrol 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: Celastrol, isoalted from Thunder God Vine/Tripterygium Wilfordiidecreases 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, 4/February/2017, 11.02 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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