Singh, Simranjit X.; Yang, Rui; Roso, Kristen; Hansen, Landon J.; Du, Changzheng; Chen, Lee H.; Greer, Paula K.; Pirozzi, Christopher J.; He, Yiping published the artcile< Purine Synthesis Inhibitor L-Alanosine Impairs Mitochondrial Function and Stemness of Brain Tumor Initiating Cells>, Name: (9Z,12Z)-Methyl octadeca-9,12-dienoate, the main research area is brain tumor mitochondrial function purine synthesis inhibitor alanosine; MTAP; adenine; alanosine; drug resistance; glioma stem cells; mitochondria; purine.
Glioblastoma (GBM) is a lethal brain cancer exhibiting high levels of drug resistance, a feature partially imparted by tumor cell stemness. Recent work shows that homozygous MTAP deletion, a genetic alteration occurring in about half of all GBMs, promotes stemness in GBM cells. Exploiting MTAP loss-conferred deficiency in purine salvage, we demonstrate that purine blockade via treatment with L-Alanosine (ALA), an inhibitor of de novo purine synthesis, attenuates stemness of MTAP-deficient GBM cells. This ALA-induced reduction in stemness is mediated in part by compromised mitochondrial function, highlighted by ALA-induced elimination of mitochondrial spare respiratory capacity. Notably, these effects of ALA are apparent even when the treatment was transient and with a low dose. Finally, in agreement with diminished stemness and compromised mitochondrial function, we show that ALA sensitizes GBM cells to temozolomide (TMZ) in vitro and in an orthotopic GBM model. Collectively, these results identify purine supply as an essential component in maintaining mitochondrial function in GBM cells and highlight a critical role of mitochondrial function in sustaining GBM stemness. We propose that purine synthesis inhibition can be beneficial in combination with the standard of care for MTAP-deficient GBMs, and that it may be feasible to achieve this benefit without inflicting major toxicity.
Biomedicines published new progress about Brain neoplasm. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Name: (9Z,12Z)-Methyl octadeca-9,12-dienoate.
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics