Natural product-derived therapy for Metastatic cancers: Shikonin, found in Zicao, among others, decreases the expression of metastasis promoters ZBTB2 and PPM1F, inhibits cell cycle progression, and suppresses migration, invasion and metastasis of cancer cells via up regulation of its target gene, 9/April/2017, 11.20 pm

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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) most of the cancer patients die due to metastasis; (iv) cancer treatment causes the highest economic loss compared to all the known causes of death worldwide, there is an urgent need to find: (i) bio-molecules that drive metastatic process; and the the way to prevent their expression; (ii) a way to activate immune system to combat cancer (Cancer immunotherapy); (ii) a cheaper alternative to the existing expensive anticancer drugs; (ii) a side-effect-free natural product-based drug; (iii) increase the therapeutic index of anticancer drugs; and (iv) a way to effectively treat and prevent metastatic progression and relapse of advanced/drug-resistant cancers.


Research findings to Therapeutic opportunity: 

A number of studies suggests that natural-product derived compound Shikonin inhibits tumor cell proliferation. However, the mechanism of action is far from clear.

This study suggests that Shikonin, by increasing the expression of its target genes, it may decrease the expression of metastasis promoters ZBTB2 (Zinc Finger And BTB Domain Containing 2) and PPM1F (Protein Phosphatase, Mg2+/Mn2+ Dependent 1F-regulator of the actin cytoskeleton)  (fig. 1).

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Shikonin functions as an antimetastasis agent

Fig1. Mechanistic insights into how Shikonin functions as an anti-metastasis agent. Shikonin inhibits the expression of metastasis promoters ZBTB2 and PPM1F via up regulation of its target genes.

Thereby, it may: (a) decrease the expression of p53 negative regulator HDM2; (b) increase the expression of tumor suppressors ARF and p53 and its target genes; (c) inhibit cell cycle progression; and (d) suppress stress fiber formation, migration, invasion and metastasis of cancer cells. Thus, pharmacological formulations encompassing “Shikonin or its analogs either alone or in combination with other anticancer drugs” may be used to inhibit the progression of invasive tumors.


Details of the research findings

Idea Proposed/Formulated (with experimental evidence) by:

Dr L Boominathan Ph.D.

Amount: $5

Undisclosed mechanistic information: How Shikonin decreases the expression of metastasis promoters ZBTB2 and PPM1F

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References

CitationBoominathan, L., Natural product-derived therapy for Metastatic cancers: Shikonin, found in Zicao, among others, decreases the expression of metastasis promoters ZBTB2 and PPM1F, inhibits cell cycle progression, and suppresses migration, invasion and metastasis of cancer cells via up regulation of its target gene, 9/April/2017, 11.20 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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