geranylgeranic acid

Definition

ChEBI: (2E,6E,10E)-geranylgeranic acid is a diterpenoid obtained by formal oxidation of the CH2OH group of (E,E,E)-geranylgeraniol to the corresponding carboxylic acid. It is a diterpenoid, a methyl-branched fatty acid, a trienoic fatty acid and an alpha,beta-unsaturated monocarboxylic acid. It is functionally related to an (E,E,E)-geranylgeraniol. It is a conjugate acid of a (2E,6E,10E)-geranylgeranate.

Biological Activity

Geranylgeranoic acid (GGA) is an isoprenoid that has been found in S. chinensis and has anticancer activity.1 It induces apoptosis in Huh7 and PLC/PRF/5 human hepatoma cells and MLE-10 transformed mouse hepatocytes, but not primary mouse hepatocytes, when used at concentrations ranging from 1 to 20 μM. GGA (10 μM) induces apoptosis in Huh7 cells via loss of the mitochondrial membrane potential and activation of interleukin-1β-converting enzyme (ICE) and cysteine protease precursor 32 (CPP32).2 It also inhibits lysine-specific demethylase 1 (LSD1; IC50 = 46.97 μM).3

References

1.Shidoji, Y., and Ogawa, H.Natural occurrence of cancer-preventive geranylgeranoic acid in medicinal herbsJ. Lipid Res.45(6)1092-1103(2004) 2.Shidoji, Y., Nakamura, N., Moriwaki, H., et al.Rapid loss in the mitochondrial membrane potential during geranylgeranoic acid-induced apoptosisBiochem. Biophys. Res. Commun.230(1)58-63(1997) 3.Sakane, C., Okitsu, T., Wada, A., et al.Inhibition of lysine-specific demethylase 1 by the acyclic diterpenoid geranylgeranoic acid and its derivativesBiochem. Biophys. Res. Commun.444(1)24-29(2014)