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Old 12-02-2014, 10:52 AM   #1
Lani
Senior Member
 
Join Date: Mar 2006
Posts: 4,776
Lightbulb reservatrol suppresses her2+ bc cell proliferation by inhibiting FASN signalling--pre

dlinical--so don't ask me the correct dose of your supplement to take,

It is unclear it holds in humans or what the dose should be. With some things, the effect of too much is the opposite of the optimal dose and noone knows either of these or if humans respond the same way as cells in petri dishes.

Still, good to know they are looking for a natural PI3k inhibitor, long the dream of Al, the husband of one of our very early "angels"


Cancer Epidemiology
Volume 38, Issue 6, Pages 765–772, December 2014
Resveratrol suppresses the proliferation of breast cancer cells by inhibiting fatty acid synthase signaling pathway

Arif Khanemailemail, Ahmad N. Aljarbou, Yousef H. Aldebasi, Syed M. Faisal1, Masood A. Khan
1Current address: National Institute of Animal Biotechnology, Hyderabad, India.
Received: January 8, 2014; Received in revised form: September 2, 2014; Accepted: September 13, 2014; Published Online: October 24, 2014
DOI: http://dx.doi.org/10.1016/j.canep.2014.09.006
Abstract
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Highlights
•The molecular connection between HER2 and FASN.
•Resveratrol inhibit FASN.
•Down-regulate Her2.
•Up-regulates the expression of Ets factor, PEA3.
•Sustained resveratrol induced-PI3K/Akt/mTOR signaling.
Abstract
In breast cancer cells, overexpression of human epidermal growth factor receptor 2 (HER2) increases the translation of fatty acid synthase (FASN) by altering the activity of PI3K/Akt signaling pathways. Cancer chemotherapy causes major side effects and is not effective enough in slowing down the progression of the disease. Earlier studies showed a role for resveratrol in the inhibition of FASN, but the molecular mechanisms of resveratrol-induced inhibition are not known. In the present study, we examined the novel mechanism of resveratrol on Her2-overexpressed breast cancer cells.

The effect of resveratrol on the growth of breast cancer cells was assessed as percent cell viability by cytotoxicity-based MTT assay and the induction of apoptosis was determined by cell-death detection ELISA and flow cytometric analysis of Annexin-V–PI binding. Western immunobloting was used to detect signaling events in human breast cancer (SKBR-3) cells.

Data showed that resveratrol-mediated down-regulation of FASN and HER2 genes synergistically induced apoptotic death in SKBR-3 cells. This concurrently caused a prominent up-regulation of PEA3, leads to down-regulation of HER2 genes. Resveratrol also alleviated the PI3K/Akt/mTOR signaling by down-regulation of Akt phosphorylation and up-regulation of PTEN expression.

These findings suggest that resveratrol alters the cell cycle progression and induce cell death via FASN inhibition in HER2 positive breast cancer.
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