nanonug
Senior Member
- Messages
- 1,709
- Location
- Virginia, USA
The prototypical inhibitor of mTOR is rapamycin. This drug has been touted by Life Extension's Bill Falloon as a way to extend healthy lifespan. mTOR inhibition leads to, among other things, an increase in autophagy. Rapamycin has also been used with apparent success in a handful of SEID patients.
Dichloroacetate is an inhibitor of pyruvate dehydrogenase kinase. It promotes the conversion of pyruvate to acetyl-CoA and, as such, appears to be an important drug in the treatment of the hypometabolic state observed by Naviaux et al in SEID patients.
What is amazing, from my point of view, is that dichloroacetate also appears to inhibit mTOR as suggested in the following four studies:
Dichloroacetate is an inhibitor of pyruvate dehydrogenase kinase. It promotes the conversion of pyruvate to acetyl-CoA and, as such, appears to be an important drug in the treatment of the hypometabolic state observed by Naviaux et al in SEID patients.
What is amazing, from my point of view, is that dichloroacetate also appears to inhibit mTOR as suggested in the following four studies:
Overexpression of pyruvate dehydrogenase kinase supports dichloroacetate as a candidate for cutaneous melanoma therapy.
Dichloroacetate induces autophagy in colorectal cancer cells and tumours
Dichloroacetate induces protective autophagy in LoVo cells: involvement of cathepsin D/thioredoxin-like protein 1 and Akt-mTOR-mediated signaling
Melanoma cell lines treated with DCA showed a shift in metabolism, that is, a decrease in glucose consumption and lactate production, downregulation of proliferation, an increase of apoptosis and a decrease in mTOR pathway activation.
Dichloroacetate induces protective autophagy in esophageal squamous carcinoma cells
Notably, the protein kinase B (Akt)-mechanistic target of rapamycin (mTOR) signaling pathway, an important negative regulator of autophagy, was demonstrated to be suppressed by DCA treatment.
Dichloroacetate induces autophagy in colorectal cancer cells and tumours
DCA induces autophagy in cancer cells accompanied by ROS production and mTOR inhibition, reduced lactate excretion, reduced k(PL) and increased NAD(+)/NADH ratio.
Dichloroacetate induces protective autophagy in LoVo cells: involvement of cathepsin D/thioredoxin-like protein 1 and Akt-mTOR-mediated signaling
Finally, we demonstrated that the Akt-mTOR signaling pathway, a major negative regulator of autophagy, was suppressed by DCA treatment.