Background:

Ginkgolic acid is an alkylphenol derivative that causes allergic skin inflammation. IC50 values of ginkgolic acid against the SUMOylation of RanGAP1-C2 are 3.0 μM. Ginkgolic Acid, a Major Component of Ginkgo biloba Extract, inhibited SUMOylation in vitro and in vivo [1].

The cytotoxicity of ginkgolic acid (15:1) in primary rat hepatocytes was lower than in HepG2 cells. Ginkgolic acid (15:1) was demonstrated less cytotoxicity in four-day-cultured primary rat hepatocytes than in 20-h cultured ones. Co-incubation with selective CYP inhibitors, α-naphthoflavone and ketoconazole, could decrease the cytotoxicity of ginkgolic acid (15:1) in primary rat hepatocytes. In agreement, pretreatment with selective CYP inducers, β-naphthoflavone and rifampin, could increase the cytotoxicity of ginkgolic acid (15:1) in HepG2 cells [2]. Ginkgolic acid inhibited the growth of tumorogenic cell lines in a dose- and time-dependent manner. Tumor cells were treated with GA for 72 h, 70.53 ± 4.54% Hep-2 and 63.5 ± 7.2% Tca8113 cells were retarded at GO/G1 phase, and the percentage of apoptosis was 40.4 ± 1.58 and 38.4 ± 1.7%, respectively [3]. In 293T cells expressing Flag-tagged SUMO, ginkgolic Acid Inhibited SUMOylation. Ginkgolic acid impaired SUMOylation by blocking the formation of an E1-SUMO thioester complex, by directly binding to E1 [1].

参考文献:
[1] Fukuda I, Ito A, Hirai G, et al.  Ginkgolic acid inhibits protein SUMOylation by blocking formation of the E1-SUMO intermediate[J]. Chemistry & biology, 2009, 16(2): 133-140.
[2] Liu Z H, Zeng S.  Cytotoxicity of ginkgolic acid in HepG2 cells and primary rat hepatocytes[J]. Toxicology letters, 2009, 187(3): 131-136.
[3] Zhou C, Li X, Du W, et al.  Antitumor effects of ginkgolic acid in human cancer cell occur via cell cycle arrest and decrease the Bcl-2/Bax ratio to induce apoptosis[J]. Chemotherapy, 2010, 56(5): 393-402.