Natural product-derived therapy for Human cancers: Shikonin, one of the main components of herb Zicao, increases the expression of mitochondrial protein LACTB, decreases levels of mitochondrial phosphatidylserine decarboxylase, alters mitochondrial lipid metabolism, and promotes differentiation of breast cancer cells via up-regulation of its target gene, 24/March/2017, 6.37 pm

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Introduction: What they say:

A study from the Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; MIT Ludwig Center for Molecular Oncology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA shows that “LACTB is a tumour suppressor that modulates lipid metabolism and cell state” This study was published in the 22 March 2017 issue of the journal “Nature” [One of the best journals in General Science with an I.F of 43 plus] by Prof. Robert A Weinberg, Zuzana Keckesova, 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 Human cancers: Shikonin, one of the main components of herb Zicao, increases the expression of mitochondrial protein LACTB, decreases levels of mitochondrial phosphatidylserine decarboxylase, alters mitochondrial lipid metabolism, and promotes differentiation of breast cancer cells via up-regulation of its target gene

Price 300

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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; (ii) cancer deaths globally are expected to be doubled in a little more than decades time; (iii) cancer treatment causes the highest economic loss compared to all the known causes of death worldwide; (iv) Breast cancer not only the most common women cancer, but also the most common invasive cancer in women; (v) Breast cancer not only metastasizes frequently, but also relapses; (vi) in 2008, breast cancer has caused more than 400000 deaths; and it is the second leading cause of cancer death in women; (vii) in 2008, breast cancer has caused economic loss of 88 billion US dollars worldwide; (viii) cancer 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 activate cancer patients immune system against tumors (Cancer immunotherapy); (ii) a cheaper alternative to the existing expensive anticancer drugs; (iii) a side-effect-free natural product-based drug; and (iv) a way to effectively treat and prevent metastatic progression and relapse of cancers.


What we infer from what they say:

Prof. Bob Weinberg’s research team has recently shown that mitochondrial protein LACTB: (1) inhibits proliferation of breast cancer cells; (2) alters mitochondrial lipid metabolism; (3) decreases the levels of mitochondrial phosphatidylserine decarboxylase (required in the synthesis of mitochondrial phosphatidylethanolamine); (4) promotes differentiation of breast cancer cells, suggesting that induction of LACTB in breast cancer cells may inhibit its proliferation.


From research findings to therapeutic opportunity :

This study suggests a natural product-derived anticancer therapy. Shikonin, one of the main components of Zicao, is known to function as an anticancer agent (fig. 1). However, the detailed mechanistic insights is yet to emerge.

Shikonin, by increasing the expression of its target genes, it may increase the expression of LACTB (fig. 1). Thereby, it may: (i) stall proliferation of breast cancer cells; (ii) alter mitochondrial lipid metabolism; (iii) decrease mitochondrial phosphatidylserine decarboxylase levels; (iv) decrease mitochondrial phosphatidylethanolamine levels; and (v) promote differentiation of breast cancer cells (fig.1).

Shikonin inducs LACTB1 and inhibits tumor progression

Figure 1. Mechanistic insights into how Shikonin increases the expression of tumor suppressor LACTB to promote differentiation of tumor cells

Thus, pharmacological formulations encompassing “Shikonin or its analogues or Shikonin in combination with other known anticancer drugs” may be used to inhibit tumor proliferation and promote tumor differentiation.


Details of the Research findings:

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

Amount: $500#

Undisclosed mechanistic information: How does Shikonin increase the expression of LACTB 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 Human cancers: Shikonin, one of the main components of herb Zicao, increases the expression of mitochondrial protein LACTB, decreases levels of mitochondrial phosphatidylserine decarboxylase, alters mitochondrial lipid metabolism, and promotes differentiation of breast cancer cells via up-regulation of its target gene, 24/March/2017, 6.37 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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