Chronic treatment of human fibroblasts cultures with diacyl-glycerol induces down-regulation of p53 functional activity.

Biochem Biophys Res Commun. 1998 Aug 10;249(1):222-5. Chronic treatment of human fibroblasts cultures with diacylglycerol induces down-regulation of p53 functional activity. Magnelli L, Cinelli M, Chiarugi V. Source Laboratory of Molecular Biology, Institute of General Pathology, Firenze, Italy. Abstract We found that many spontaneous human tumors exhibit increased levels of endocellular diacylglycerol (DAG) which is synthesized de novo as a byproduct of glycolysis. It has been shown that DAG mimics phorbol esters as a full tumor promoter in mouse skin carcinogenesis. A short term DAG treatment activates protein kinase C (PKC), while a long term "chronic" treatment down-regulates PKC. We show here that chronic treatment of human fibroblast with DAG induces p53 down-regulation and inhibition of p53 functional activity, and protection from UV-induced apoptosis. As PKC phosphorylation is necessary for p53 functional activity, we propose that chronic DAG treatment mimics the same event occurring in vivo for the effect of glycolysis in tumor progression. PMID: 9705861 [PubMed - indexed for MEDLINE]