Rabbit Anti-Human MTOR Polyclonal Antibody

Prostate cancer (PC) is one of the major impediments affecting men, which leads approximately 31,620 deaths in both developing and developed countries. Although some chemotherapy drugs have been reported for prostate cancer, they are not effective due to the lack of safety, efficacy and low selectivity. Hence, the novel alternative anticancer agents with remarkable effect are highly appreciable. Natural plants contain several bio-active compounds which have been traditionally used for the various medical treatments. Particularly, naringin is a natural bio-active compound commonly found in the citrus fruits, which have shown numerous biological activities. Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene, which activates both lipid phosphates and protein phosphates. The PTEN gene is negative regulator of PI3K/AKT/mTOR pathways, since, this signaling pathway play an essential role in the cell survival, proliferation and migration. In the presentin silicoinvestigation, structure based virtual screening, molecular docking, molecular dynamics simulation and Adsorption, Distribution, Metabolism, Excretion (ADME) prediction were employed to determine the binding affinity, stability and drug likeness properties of top ranked screened compounds and naringin, respectively. The results revealed that the complex has good molecular interactions, binding stability (peak between 0.3 and 0.4 nm) and no violations in the Lipinski Rule of 5 in naringin, but the screened compounds violated the drug likeness properties. From thein silicoanalyses, it is identified that naringin compound might assist in the development of novel therapeutic candidate against prostate cancer. Communicated by Ramaswamy H. Sarma

The Pro47Ser variant of p53 (S47) exists in African-descent populations and is associated with increased cancer risk in humans and mice. Due to impaired repression of the cystine importer Slc7a11, S47 cells show increased glutathione (GSH) accumulation compared to cells with wild -type p53. We show that mice containing the S47 variant display increased mTOR activity and oxidative metabolism, as well as larger size, improved metabolic efficiency, and signs of superior fitness. Mechanistically, we show that mTOR and its positive regulator Rheb display increased association in S47 cells; this is due to an altered redox state of GAPDH in S47 cells that inhibits its ability to bind and sequester Rheb. Compounds that decrease glutathione normalize GAPDH-Rheb complexes and mTOR activity in S47 cells. This study reveals a novel layer of regulation of mTOR by p53, and raises the possibility that this variant may have been selected for in early Africa.