The anti-tumor effect and mechanisms of action of penta-acetyl geniposide

Gardenia, the fruit of Gardenia jasminoides Ellis, has been widely used to treat liver and gall bladder disorders in Chinese medicine. It has been shown recently that geniposide, the main ingredient of Gardenia Fructus, exhibits the anti-tumor effect. In this review, we discuss the anti-tumor effect and possible mechanisms of a derivative from Gardenia Fructus, penta-acetyl geniposide ((Ac)(5)GP). It has been demonstrated that (Ac)(5)GP plays more potent roles than geniposide in chemoprevention. (Ac)5GP decreased DNA damage and hepatocarcinogenesis induced by aflatoxin B-1 (AFB(1)) by activating the phase II enzymes glutathione S-transferase (GST) and GSH peroxidase (GSH-Px). It reduced the growth and development of inoculated C6 glioma cells especially in pre-treated rats. In addition to the preventive effect, (Ac)(5)GP exerts its actions on apoptosis and growth arrest. Treatment of (AC)5GP caused DNA fragmentation of glioma cells. (AC)5GP induced sub-G(1) peak through the activation of apoptotic cascades PKC delta/JNK/Fas/ caspase8 and caspase 3. Besides, p53/Bax signaling was suggested to be involved in (AC)(5)GP-induced apoptosis, though its downstream cascades needs further clarified. (AC)(5)GP has also been shown to inhibit DNA synthesis of tumor cells. It arrested cell cycle at G(0)/G(1) by inducing the expression of p21, thus suppressing the cyclin D-1/cdk4 complex formation and the phosphorylation Of E2F. The phosphorylation status of p53 on serine 392 correlated with the process of growth arrest. Evidences from the in vivo experiments showed that (AC)(5)GP is not harmful to liver, heart and kidney. In conclusion, (AC)(5)GP is highly suggested to be an anti-tumor agent for development in the future.