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See Latest ArticlesInhibition of de novo purine synthesis in human prostate cells results in ATP depletion, AMPK activation and induces senescence
The Prostate, 05/13/09
Obajimi O et al. - LNCaP cells primarily depend upon de novo while RWPE-1 cells largely favor salvage synthesis for maintenance of their ATP pools. With AG2034 treatment, ATP synthesis via hypoxanthine salvage is insufficient to support growth of LNCaP but enough to restore ATP levels and support RWPE-1 growth. The anti-proliferative effect of AG2034 involves increasing phosphorylation of AMPK. These results indicate that AG2034 activates p53 and AMPK mediating the induction of signaling pathways leading to senescence.
Oluwakemi Obajimi, 05/20/09
Androgen-dependent prostate cancer cells, LNCaP, depend primarily on the de novo process while non-tumorigenic, androgen-sensitive prostate cells, RWPE-1, largely favor salvage synthesis for maintenance of their ATP pools. With the treatment of these cells with AG2034, a classical antifolate shown to be an excellent inhibitor of glycinamide ribonucleotide formyltransferase, ATP synthesis through hypoxanthine salvage is insufficient to support the growth of LNCaP cells but in RWPE-1 cells is enough to restore ATP levels and support growth. Also, the anti-proliferative effect of AG2034 involves increasing phosphorylation levels of AMP-activated protein kinase (AMPK). In summary, AG2034 activates p53 and AMPK and mediates the induction of signaling pathways leading to senescence. |
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