Natural product-derived combo therapy for ACAT1-overexpressing Human cancers: Curcumin and (6)-gingerol (6G) combo, one of the main components of Turmeric and Ginger, respectively, 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, 24/November/2015, 2.57 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-derived combo therapy for ACAT1-overexpressing Human cancers: Curcumin and (6)-gingerol (6G) combo, one of the main components of Turmeric and Ginger, respectively, 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 suggests 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:

I have published earlier that 6-gingerol (6G), isolated from Ginger, suppresses Pyruvate dehydrogenase complex (PDC) formation and inhibits the progression of ACAT-overexpressing tumors (Figure 1).

This study suggests, for the first time, that Curcumin, 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 (Figure 2).

6-gingerol

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

curcumin க்கான பட முடிவு

Figure 2. Curcumin, found in Turmeric, suppresses Pyruvate dehydrogenase (PDH) and PDH phosphatase expression and inhibits the progression of ACAT-overexpressing tumors

gingerol-plus-curcumin-a-recipie-for-anticancer-therapy

Figure 3. Cucumin and (6)-gingerol (6G) combo: A recipe for anticancer therapy: Super -inhibition of ACAT1 by Cucumin and (6)-gingerol (6G) combo may inhibit the progression of human cancers that overexpress ACAT.Ginger root

Isorhapontigenin, isolated from  Aiphanes Aculeata, Norway/Sitka/White Spruce ,  among others, extends mammalian lifespan via up-regulation of BuBR1

Turmeric flowers

Turmeric

Turmeric. Curcumin, isolated from Turmeric, inhibits tumor growth and the progression of ACAT-dependent cancers.

Indian Ginger Flowers க்கான பட முடிவு

Ginger Flowers

ginger

Ginger root


Thus, pharmacological formulations encompassing Curcumin (figure 1) or its analogues or Curcumin plus (6)-gingerol (6G) combo (figure 3) or Curcumin 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.

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

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References:

Citation: Boominathan, L., Natural product product-derived combo therapy for ACAT1-overexpressing Human cancers: Curcumin and (6)-gingerol (6G) combo, one of the main components of Turmeric and Ginger, respectively, 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, 24/November/2015, 2.57 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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