geranylgeranic-acid and squalestatin-1

Geranylgeranoic acid (GGA) has been reported to induce autophagic cell death via upregulation of lipid-induced unfolded protein response in several human hepatoma-derived cell lines, and its 4,5-didehydro derivative has been developed as a preventive agent against second primary hepatoma in clinical trials. We have previously reported that GGA is a natural diterpenoid synthesized in several medicinal herbs. Here, we provide unequivocal evidence for de novo GGA biosynthesis in mammals. First, with normal male Wistar rats, the levels of GGA in liver were found to be far greater than those in other organs analyzed. Second, we demonstrated the metabolic GGA labeling from the

Topics: Animals; Bridged Bicyclo Compounds, Heterocyclic; Cell Death; Cell Line, Tumor; Diterpenes; Male; Mevalonic Acid; Rats; Rats, Wistar; Tricarboxylic Acids