Natural product-derived therapy for metastatic prostate cancer: Honokiol, isolated from Magnolia Grandiflora, inhibits the expression of CDC42, CDC42EP3, RAC1 and ARPC5, and GAS6, suppresses the expression of stem cell molecules CD44 and EZH2, promotes epithelial phenotype, suppresses tumorigenesis, migration, invasion, stem cell regeneration and metastasis via up regulation of its target gen, 10/March/2017, 8.53 pm

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Introduction: What they say:

A study from the Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Science Park, Texas 78957, USA shows that “MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes.” This study was published in the 23 January 2017 issue of the journal “Nature communications”

by Prof. G Dean Tan, Liu C, 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 metastatic prostate cancer: Honokiol, isolated from Magnolia Grandiflorainhibits the expression of CDC42, CDC42EP3, RAC1 and ARPC5, and GAS6, suppresses the expression of stem cell molecules CD44 and EZH2, promotes epithelial phenotype, suppresses tumorigenesis, migration, invasion, stem cell regeneration and metastasis via up 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) each year 176,000 cases of prostate cancer are identified in the US; and about 28,000 of them will die; (iii) about 70% of Prostate cancers are deficient in tumor suppressor gene PTEN, the second most mutated gene in cancer, next to tumor suppressor Tp53; (iv) cancer deaths globally are expected to be doubled by 2030; (v) 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 (Cancer immunotherapy); (ii) anticancer drugs that inhibit cancer stem cells that aid in tumor relapse and drug resistance; (iii) a cheaper alternative to the existing expensive anticancer drugs; (iv) a side-effect-free natural product-based drug; (v) increase the therapeutic index of anti-cancer drugs; and (vi) a way to effectively treat and prevent metastatic progression and relapse of advanced/drug-resistant cancers.


What we infer from what they say:

Prof. Dean Tan’s research team has recently shown that overexpression of MiR-141: (1) promotes strong epithelial phenotype; (2) promotes a partial loss of mesenchymal phenotype; (3) suppresses the expression of Rho GTPase family members, including CDC42, CDC42EP3, RAC1, ARPC5 and Gas6; (4) inhibits the expression of stem cell molecules such as CD44/Pgp-1 and EZH2; (5) inhibits cancer stem cell properties including holoclone and sphere formation; and (6) inhibits invasion, migration, tumour stem cell regeneration and metastasis.


From research findings to therapeutic opportunity :

This study suggests a vitamin-based therapy for prostate cancer metastasis. Honokiol  has been shown to function as an anticancer agent (fig. 1). However, the detailed mechanistic insights is yet to emerge.

Honokiol induces miR-141 expression and inhibit prostate cancer progression

Figure 1. Mechanistic insights into how Honokiol suppresses the expression of CDC42, CDC42EP3, RAC1, ARPC5, Gas6, CD44/Pgp-1 and EZH2 and inhibits prostate cancer metastasis

Honokiol, by increasing the expression of its target genes, it may decrease the expression of CDC42, CDC42EP3, RAC1, ARPC5 and Gas6 (fig. 1). Thereby, it may: (i) decrease the expression of stem cell molecules such as CD44/Pgp-1 and EZH2; (ii) enforce strong epithelial phenotype on poorly differentiated cancer cells; (iii) inhibit cancer stem cell properties; (iv) suppress tumor stem cell regeneration; and (v) inhibit invasion, migration and metastasis.

Thus, pharmacological formulations encompassing Honokiol or its analogues either alone or in combination with other known anticancer drugs” may be used to inhibit metastatic progression and stem cells properties of prostate cancers.[easy_payment currency=”USD”]


Details of the Research findings:

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

Amount: $300#

Undisclosed mechanistic information: How does Honokiol decrease the expression of stem cell proteins to inhibit metastatic prostate cancer progression?

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References:

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Citation: Boominathan, L., Natural product-derived therapy for metastatic prostate cancer: Honokiol, isolated from Magnolia Grandiflorainhibits the expression of CDC42, CDC42EP3, RAC1 and ARPC5, and GAS6, suppresses the expression of stem cell molecules CD44 and EZH2, promotes epithelial phenotype, suppresses tumorigenesis, migration, invasion, stem cell regeneration and metastasis via up regulation of its target gen, 10/March/2017, 8.52 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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