Cancer and Central Nervous System

DHPS is of particular interest in cancer and in the central nervous system, as it is upregulated in cancers due to its involvement in cell proliferation.

• Bidirectional regulation between WDR83 and its natural antisense transcript DHPS in gastric cancer. (PMID: 22491477,(ncbi.nlm.nih.gov)) Su W.Y. … Fang J.Y. Cell Res. 2012 3 64
  • DHPS regulates the expression of WDR83 mRNA and protein, and WDR83 also regulates DHPS by antisense pairing. This bidirectional expression is possible because WDR83 and DHPS can form an RNA duplex at overlapping 3′ untranslated regions, which increase stability. WDR83 and DHPS are upregulated simultaneously and correlated positively in gastric cancer, promoting cell proliferation, and this effect was observed in other cancers.
• Expression of eukaryotic initiation factor 5A and hypusine forming enzymes in glioblastoma patient samples: implications for new targeted therapies. (PMID: 22927971,(ncbi.nlm.nih.gov)) Preukschas M. … Balabanov S. PLoS ONE 2012 3 64
  • DHPS, eIF-5A, and DOHH are highly overexpressed in glioblastoma patient samples. GC7 is a specific DHPS-inhibitor that showed a strong antiproliferative effect in glioblastoma cell lines, while normal human astrocytes were not affected. This research shows that stable knockdown of eIF-5A and DHPS by short hairpin RNA (shRNA) could mimic the antiproliferative effects of GC7.
• Neuronal growth and survival mediated by eIF5A, a polyamine-modified translation initiation factor. (PMID: 17360499,(ncbi.nlm.nih.gov)) Huang Y. … Snyder S.H. Proc. Natl. Acad. Sci. U.S.A. 2007 22 64
  • When researchers prevented hypusine formation, the NGF-elicited augmentation of neurite outgrowth and PC12 cell survival were blocked. In brain cultures, inhibition of hypusine formation also inhibits neuronal process extension.
• Aminohexanoic hydroxamate is a potent inducer of the differentiation of mouse neuroblastoma cells. (PMID: 11098085,(ncbi.nlm.nih.gov)) Lu J. … Chen K.Y. Cancer Lett. 2000 22 64
  • Used GC7 as a prototype to synthesize and test three classes of diamine analogs as potential inhibitors for DHPS: guanidino-,pyrimidino-, and hydroxamate derivatives. Among all the compounds tested, GC7 remained to be the most potent inhibitor for DHPS. N,N0-bispyrimidino-1,9-diaminononane, is a poor inhibitor of DHPS.