Background: The isothiocyanate sulforaphane (SFN) has multiple protein targets in mammalian cells, affecting processes of fundamental importance for the maintenance of cellular homeostasis, among which are those regulated by the stress response transcription factor nuclear factor erythroid 2 p45-related factor 2 (NRF2) and the serine/threonine protein kinase mechanistic target of rapamycin (mTOR). Whereas the way by which SFN activates NRF2 is well established, the molecular mechanism(s) of how SFN inhibits mTOR is not understood.
Hypothesis/purpose: The aim of this study was to investigate the mechanism(s) by which SFN inhibits mTOR STUDY DESIGN AND METHODS: We used the human osteosarcoma cell line U2OS and its CRISPR/Cas9-generated NRF2-knockout counterpart to test the requirement for NRF2 and the involvement of mTOR regulators in the SFN-mediated inhibition of mTOR.
Results: SFN inhibits mTOR in a concentration- and time-dependent manner, and this inhibition occurs in the presence or in the absence of NRF2. The phosphatidylinositol 3-kinase (PI3K)-AKT/protein kinase B (PKB) is a positive regulator of mTOR, and treatment with SFN caused an increase in the phosphorylation of AKT at T308 and S473, two phosphorylation sites associated with AKT activation. Interestingly however, the levels of pS552 β-catenin, an AKT phosphorylation site, were decreased, suggesting that the catalytic activity of AKT was inhibited. In addition, SFN inhibited the activity of the cytoplasmic histone deacetylase 6 (HDAC6), the inhibition of which has been reported to promote the acetylation and decreases the kinase activity of AKT.
Conclusion: SFN inhibits HDAC6 and decreases the catalytic activity of AKT, and this partially explains the mechanism by which SFN inhibits mTOR.
This is great. I am interviewing the president of Kuli Kuli, provider of Moringa (source of sulforaphane) in October. I can explore further. Any other questions I should ask?
They are a local Oakland success story … that is helping a lot of people in Africa also. I think it was started by some men and women who identified the opportunity while they were in the peace corp. in Africa. I’ve got a friend who has consulted with them, they sound like a really good company. But… I suspect they don’t know that much about the science behind it, other than knowing that its “good for you”…
I would ask them about the scientists that they interact with that know the NRF2 pathway extremely well, and perhaps interview one of those people.
I would also ask how / if they can make it taste better? I like the purported health benefits of Moringa powder, but have to say the taste is pretty bad, and its hard to mix into a smoothie without a lot of better tasting things.
Cruciferous vegetables have sulphoraphanes, with broccoli having the most. Fresh broccoli sprouts has by far most of all. I eat 50 - 100 gram of the latter whenever a new batch is ready. Sulphoraphanes may be anti- cancer too.
“Research shows that taking moringa powder every day, even 50 mg/kg of body weight, successfully reduces oxidative stress in the body–that’s the equivalent of approximately 1.5 teaspoons for someone weighing 150 pounds. [5] On the other end of the spectrum, animal studies using Moringa oleifera extract revealed delayed tumor growth and increased life span at a dosage of 500 mg/kg of body weight.”
I use Jarrow BroccoMax. I had also used Life Extension’s Broccoli and Cruciferous Blend for a while (recently discontinued, I think) but the main ingredient was glucoraphanin rather than sulforaphane.