Natural product therapy for ACAT1-overexpressing Human cancers: (6)-gingerol (6G), one of the main components of Ginger, inhibits Mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) expression, acetylation of Pyruvate dehydrogenase (PDH) and PDH phosphatase, pyruvate dehydrogenase complex (PDC) formation and tumor growth via down regulation of its target gene, 22/November/2015, 7.26 pm

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Introduction: What they say

A study from the Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA shows that “Tetrameric Acetyl-CoA Acetyltransferase 1 Is Important for Tumor Growth.” This research paper was published in the 17 November 2016 issue of the journal “Molecular cell” [One of the best research journals in General Biology with an I.F of 13.958] by Prof. Jing Chen, Jun Fan 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 therapy for ACAT1-overexpressing Human cancers: (6)-gingerol (6G), one of the main components of Ginger, inhibits Mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) expression, acetylation of Pyruvate dehydrogenase (PDH) and PDH phosphatase, pyruvate dehydrogenase complex (PDC) formation and tumor growth via down regulation of its target gene

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From Significance of the study to Public health relevance:

Given that: (1) ACAT1 (Acetyl-Coenzyme A acetyltransferase 1) is overexpressed in a number of cancers, including aggressive prostate cancer and estrogen receptor negative breast cancer; (2) overexpression of ACAT in cancer cells correlates with poor patient survival; (3) our understanding is incomplete in terms of molecular targets and the oncogenic/malignant pathways involved in ACAT-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 ACAT-overexpressing cancers.


What is known?

A number of studies suggest that ACAT is overexpressed in cancers, such as, aggressive prostate cancer and estrogen receptor negative breast cancer. However, the mechanistic basis of its deregulation remains largely unclear.

Prof. Chen’s research team has recently shown that: (1) tetrameric ACAT1 is commonly upregulated in cancer; (2) tetrameric ACAT1 is phosphorylated and stabilized by Y407 phosphorylation; (3) Arecoline hydrobromide (AH) disrupts tetrameric ACAT1 complex and abolishes Y407 phosphorylation; (4) AH functions as an inhibitor of ACAT tetramer in cancer cells; and (5) AH inhibits cancer cell proliferation and tumor growth.


From  Research findings to Therapeutic opportunity:

This study suggests, for the first time, a natural product based therapy for ACAT-overexpressing tumors. (6)gingerol (6G), by increasing the expression of its target gene, it may decrease the expression of ACAT. Thereby, it may: (1) inhibit acetylation of Pyruvate dehydrogenase (PDH) and PDH phosphatase; (2) suppress pyruvate dehydrogenase complex (PDC) formation; (3) decrease glycolysis; (4) increase Oxidative phosphorylation; (5) inhibit cholesterol esterification; and (6) inhibit tumor growth and the progression of ACAT-dependent cancers.

6-gingerol

Figure1. 6-gingerol (6G), isolated from Ginger, suppresses Pyruvate dehydrogenase complex (PDC) formation and inhibits the progression of ACAT-overexpressing tumors

ginger

Ginger root

Ginger Flowers

Ginger Flowers

Thus, pharmacological formulations encompassing (6)-gingerol (6G) or its analogues or (6)-gingerol (6G) plus any of the known anti-cancer compounds that inhibit the expression of ACAT may be used to treat ACAT-overexpressing tumors, such as aggressive prostate cancer and estrogen receptor negative breast cancer.


Details of the research findings

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

Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/

Undisclosed information: How (6)-gingerol (6G) inhibits acetylation of Pyruvate dehydrogenase (PDH) and PDH phosphatase

# Research cooperation


References:

Citation: Boominathan, L., Natural product therapy for ACAT1-overexpressing Human cancers: (6)-gingerol (6G), one of the main components of Ginger, inhibits Mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) expression, acetylation of Pyruvate dehydrogenase (PDH) and PDH phosphatase, pyruvate dehydrogenase complex (PDC) formation and tumor growth via down regulation of its target gene, 22/November/2015, 7.26 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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