Natural product-based therapy for Metastatic tumors: Formononetin, an isoflavone found in the roots of astragalus membranaceus, Trifolium pratense, Glycyrrhiza glabra, and Pueraria lobata, increases the expression of metastasis suppressor gene TPM1 and inhibits invasion, migration and metastasis of tumor cells via down regulation of its target gene, 1/February/2017, 5. 41 pm

From Significance of the study to Public health relevance: 

Given that: (1) Cancer suppressor p53 is mutated in more than 50% of human cancers of different tissue origin; (2) p53 pathway is altered in about 80% of tumors.; (3) our understanding is incomplete in terms of molecular targets and the oncogenic/malignant pathways involved in mutant p53-overexpressing tumors; (4) cancer causes the highest economic loss compared to all the known causes of death worldwide; and (5) cancer causes the considerable economic loss worldwide, there is an urgent need to find: (i) a cheaper alternative to the existing expensive drugs; (ii) a side-effect-free natural product-based drug; and (iii) a way to effectively treat and stall metastatic progression; and relapse of metastatic/drug-resistant human cancers.

From therapeutic strategy to Research Findings:

(i) Therapeutic strategy: 

This study suggests a therapeutic strategy for inhibiting the progression of metastatic cancers. By activating the expression of metastatic suppressor gene in invasive tumor cells, one may impede their progression.

(ii) Research findings:  

A number of studies suggests that Formononetin prevents tumor progression and metastasis. However, the detailed mechanistic insights is yet to emerge. This study suggests, for the first time, that Formononetin, by decreasing the expression of its target gene, it may not only increase the expression of tumor suppressors genes, but also increase a number of metastatic suppressor genes, including TPM1. Thereby, it may inhibit the migration and invasion of metastatic cancer cells (figure 1-5).

Figure 1. The chemical structure of Formononetin. Formononetin functions as an antimetastatic agent by increasing the expression of TPM1, via down regulation of its target gene

Fig 2. Astragalus membranaceus. Mechanistic insights into how Formononetin functions as an anticancer/antimetastatic agent. Formononetin, one of the main components of Astragalus membranaceus, among others, as indicated below, by activating metastatic suppressor genes such as TPM1, it may inhibit the progression of metastatic human cancers.

Fig 3. Trifolium pratense

Fig4. Pueraria lobata

Fig5. Glycyrrhiza glabra (Liquorice)

Therapeutic opportunity:

Given the ability of Formononetin to induce the expression of tumor suppressor gene PTEN and the metastasis suppressor gene TPM1, pharmacological formulations encompassing “Formononetin or its analogues or Formononetin plus any of the known anticancer agents” may be used to inhibit the progression of metastatic tumors.

Details of the research findings: 

Idea Proposed/Formulated by: Dr L Boominathan Ph.D.

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Undisclosed mechanistic information: How does Formononetin increase the expression of metastatic suppressor gene TPM1?

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References:

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Citation: Boominathan, L., Natural product-based therapy for Metastatic tumors: Formononetin, an isoflavone found in the roots of astragalus membranaceus, Trifolium pratense, Glycyrrhiza glabra, and Pueraria lobata,  increases the expression of metastasis suppressor gene TPM1 and inhibits invasion, migration and metastasis of tumor cells via down regulation of its target gene, 1/February/2017, 5. 41 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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