Introduction: What they say:
A study from the Department of Biochemistry-Molecular Biology, Franklin College of Arts and Sciences, The University of Georgia, Athens, Georgia 30602, USA; and The University of Georgia Cancer Center, The University of Georgia, Athens, Georgia 30602, USA shows that “Cancer progression by reprogrammed BCAA metabolism in myeloid leukaemia”. This study was published, in the 25 May 2017 issue of the journal “Nature” [One of the best journals in General Science with an I.F of 43 plus] by Prof. Ito, Hattori A, 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 Chronic Myeloid leukaemia (CML): Honokiol, isolated from Magnolia Grandiflora (MG), decreases the expression of Musashi2, inhibits cytosolic aminotransferase BCAT1 expression, decreases the intracellular production of BCAAs (Branched-chain amino acids), increases the expression of tumor suppressor genes, promotes differentiation of CML cells, and inhibits cancer progression in Myeloid leukemia 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 cannot be cured by current treatment methodologies (and hence they will die); (ii) cancer deaths globally are expected to be doubled by next decade or so; (iii) cancer treatment causes the highest economic loss compared to all the known causes of death worldwide; (iv) Acute myeloid leukemia (AML) is one of the most predominant leukemias among all adult leukemias, while Chronic myeloid leukemia (CML) accounts for about little less than 10% of all leukemias; (v) each year about 10,500 and 2900 new cases of AML are reported in the US and the UK, respectively; (vi) cure rates of AML ranges from 20-45% only, there is an urgent need to find: (i) a way to activate patients immune system (Cancer immunotherapy); (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 is known:
Prof. Takahiro Ito’s research team has recently shown that: (1) the cytosolic aminotransferase BCAT1 (branched-chain amino acid transaminase 1) is upregulated in CML; (2) CML cells have increased levels and production of BCAA (Branched chain amino acids); (3) inhibition of BCAT1 in leukemic cells promotes cellular differentiation; and (4) Musashi2, which functions as an upstream activator of BCAT1, promotes leukemic progression, suggesting that combined inhibition of Musashi2 & BCAT1 in CML may make it less aggressive, slow growing and amenable to anticancer drug treatment.
From research findings to therapeutic opportunity :
This study suggests a natural product-derived anticancer therapy for promoting cellular differentiation in ML (Myeloid leukaemia). Honokiol is known to function as an anticancer agent (fig. 1). However, the detailed mechanistic insights is yet to emerge.
Honokiol, by increasing the expression of its target genes, it may decrease the expression of Musashi2 & BCAT1 (fig. 1). Thereby, it may: (i) decrease the expression of oncogenic MiR-17-92; (ii) increase the expression of tumor suppressor genes, such as PTEN, NUMB and INK4a; (iii) decrease BCAA (Branched chain amino acid) production; (iv) promote differentiation of leukemic cells; (v) slow down CML and de novo acute myeloid leukaemia(AML) growth; and (vi) inhibit cancer progression in Myeloid leukemia (fig.1).
Thus, pharmacological formulations encompassing “Honokiol or an active compound isolated from it, either alone or in combination with other known TKI drugs,” (fig. 2) may be used to slow down CML and AML growth.
Details of the Research findings:
Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.
Undisclosed mechanistic information: How does Honokiol decrease the expression of Musashi2 & BCAT1 to inhibit ML growth?
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Citation: Boominathan, L., Natural product-derived therapy for Chronic Myeloid leukaemia (CML): Honokiol, isolated from Magnolia Grandiflora (MG), decreases the expression of Musashi2, inhibits cytosolic aminotransferase BCAT1 expression, decreases the intracellular production of BCAAs (Branched-chain amino acids), increases the expression of tumor suppressor genes, promotes differentiation of CML cells, and inhibits cancer progression in Myeloid leukemia via up-regulation of its target gene, 29/May/2017, 11.43 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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