Natural product-derived therapy for triple-negative breast tumors: Withaferin A, isolated from Withania somnifera/Ashwagandha and Acnistus arborescens among others, increases the levels of cell cycle inhibitor, p27, inhibits pro-survival pathways mediated by c-Myc, and inhibits the progression of triple-negative breast cancer via up-regulation of its target gene, 2/December/2015, 6.32 pm

Natural product-derived therapy for Myocardial Infarction: Emodin (6-methyl-1,3,8-trihydroxy anthraquinone), found in Polygonum multiflorum, and Japanese knotweed among others, inhibits DNA damage responses, and telomere shortening, and promotes cardiomyocyte survival after myocardial infarction via up-regulation of PNUTS, 2/December/2016, 12.15 pm
December 2, 2016
Natural product-derived anti-ageing therapy: Shikonin, the major component of Zicao (also known as purple gromwell, the dried root of Lithospermum erythrorhizon), activates autophagy and extend lifespan via up regulation of its target gene, 2/December/2016, 7.14 pm
December 2, 2016
Show all

Introduction: What they say

A study from the Department of Cell and Tissue Biology, University of California, San Francisco (UCSF), San Francisco, California, USA shows thatPIM1 kinase inhibition as a targeted therapy against triple-negative breast tumors with elevated MYC expression”

Another study, carried out in parallel, from the Breast Cancer Now Research Unit, Division of Cancer Studies, Faculty of Life Sciences and Medicine, King’s College London, Guy’s Hospital, London, UK and Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research, London, UK. shows that “PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer”

These research papers were published in the 24 October 2016 issue of the journal “Nature Medicine” [the number 1 research journal in General Medicine with an I.F of 30.357+] by Profs. Andrei Goga’s (USA) and Andrew N Tutt’s (UK) research teams.


What we say:

On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Natural product Withaferin A increases the levels of cell cycle inhibitor, p27, inhibits pro-survival pathways mediated by c-Myc, and inhibits the progression of triple-negative breast cancer via upregulation of its target gene

price-100

[easy_payment currency=”USD”]


From Significance of the study to Public health relevance:

Given that: (1) Breast cancer not only the most common women cancer, but also the most common invasive cancer in women; (2) Breast cancer not only metastasizes frequently, but also relapses; (3) Out of the all the known breast cancer subtypes, triple-negative–for estrogen receptor, the progesterone receptor and the HER2 receptor–breast cancers is one of the hardest to treat, as we lack details of molecular targets and the oncogenic/malignant pathways involved; (4) in 2008, breast cancer has caused more than 400000 deaths; and it is the second leading cause of cancer death in women; (5) in 2008, breast cancer has caused economic loss of 88 billion US dollars worldwide; (6) cancer causes the highest economic loss compared to all the known causes of death 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 triple-negative drug-resistant breast cancer.


What is known?

Prof. Gaga’s research team has recently shown that triple-negative breast tumors: (1) contain increased levels of c-Myc; and (2) contain increased levels of PIM1 kinase. Further, they showed that inhibition of PIM1 kinase, in c-Myc over-expressing triple-negative breast tumors, not only regressed, but also stalled the progression triple-negative breast tumors, via induction of cell cycle inhibitor p27.

In parallel, Prof. Andrew N Tutt’s research team has shown that triple-negative breast cancers (TNBCs): (1) have high copy number and the expression of oncoprotein PIM1; (2) contain increased levels of pro-survival protein Bcl-2; and (2) contain increased levels of c-Myc and its target gene Mcl-1. Further, they showed that knockdown/ depletion of PIM1 in TNBC’s resulted in: (1) decreased expression of Bcl-2; and (2) increased chemosensitivity.


From Research findings to Therapeutic opportunity

This study suggests, for the first time, a natural product based therapy for triple-negative breast cancer. Withaferin A, by decreasing the expression of its target gene, it may increase the expression of cell cycle inhibitor, p27. Thereby, it may inhibit: (1) transcriptional activity of oncogenic c-Myc; (2) PIM1 expression; (3) pro-survival protein Bcl-2 and c-Myc and its target gene MCL1 expression; and (4) the progression of triple-negative breast cancer. Thus, pharmacological formulations encompassing Withaferin A or its analogues or Withaferin A plus any of the known anticancer drugs in use may be used to treat triple-negative breast tumors.

Withaferin A, isolated from Withania somnifera (Ashwagandha), inhibits aberrant lipid biosynthesis in cancer cells via down-regulation of ACLY

Figure 1. Withania somnifera/Ashwagandha. Withaferin A, isolated from Withania somnifera (Ashwagandha), inhibits the progression of triple-negative breast tumors via down-regulation of oncoproteins c-Myc, PIM1, Bcl-2, and Mcl-1

acnistus-arborescens

Figure 2 Acnistus arborescens. Withaferin A is also found in Acnistus arborescens

 

WithaferinA2DACS.svg

Fig.3. Withaferin A. Picture credit: Wikipedia

 


Details of the research findings: 

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

Amount: $100

Undisclosed mechanistic information: How Withaferin A increases the expression of cell cycle inhibitor and the tumor suppressor p27 and decreases the expression of oncoproteins c-Myc, Mcl-1, Bcl-2 and PIM1

# Research cooperation

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

# Research cooperation

For purchase and payment details, you may reach us at admin@genomediscovery.org


References:

Citation: Boominathan, L.,  Natural product-derived therapy for triple-negative breast tumors: Withaferin A, isolated from Withania somnifera/Ashwagandha and Acnistus arborescens among others, increases the levels of cell cycle inhibitor, p27, inhibits pro-survival pathways mediated by c-Myc, and inhibits the progression of triple-negative breast cancer via up-regulation of its target gene, 2/December/2015, 6.32 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

Web: http://genomediscovery.org or http://newbioideas.com

Courtesy: When you cite drop us a line at info@genomediscovery.org

Comments are closed.