Search

Background We investigated whether retroviral p53 transfection could enhance growth inhibition and chemosensitivity in a p53 mutant papillary thyroid cancer cell line (NPA). Methods NPA cells were transfected with either LXSN/p53 or mock infection in the presence of Adriamycin. Gene expression was confirmed by western blotting. Nude mice were injected subcutaneously with NPA cells after transfection with either LXSN/p53 or mock infection on opposite sides, and the tumor growth was compared. Results There was a dose-dependent inhibition of tumor growth with LXSN/p53 transfection. Tumor growth was inhibited more by p53 gene transfection relative to mock transfection in the presence of Adriamycin. Conclusion These treatment modalities could be beneficial in the treatment of p53 mutant positive thyroid cancers. © 2001 John Wiley & Sons, Inc. Head Neck 23: 223–229, 2001.

Nicotinamide at millimolar concentrations affects cell survival in various conditions, and is being utilized therapeutically in many human diseases. However, the effect of an acute treatment of nicotinamide at such high dose on gene expression and cellular metabolism has rarely been determined previously. In this study, we found that levels of O -N-acetylglucosamin(O-GlcNAc)ylated proteins including Sp1 acutely decreased upon treatment of 10 mM nicotinamide. Concomitantly, Sp1 protein level decreased rapidly through accelerated proteasome-mediated proteolysis. Co-treatment of glucosamine or 2-deoxyglucose, which inhibits protein deGlcNAcylation, effectively blocked the decrease induced by nicotinamide. Interestingly, the decline in the levels of Sp1 and protein O-GlcNAcylation was only transient lasting for two days post treatment, and this pattern matched closely the rapid fluctuation of the cellular [NAD+]. Our results suggest a possible link between cellular nicotinamide metabolism and protein O-GlcNAcylation, and an existence of cellular [NAD+] homeostasis.