Anti-hepatoma activity and mechanism of ursolic acid and its derivatives isolated from Aralia decaisneana.
OBJECTIVE
To investigate the anti-tumor activity of ursolic acid (UA) and its derivatives isolated from Aralia decaisneana on hepatocellular carcinoma both in vitro and in vivo.


METHODS
In vivo cytotoxicity was first screened by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. Morphological observation, DNA ladder, flow cytometry analysis, Western blot and real time PCR were employed to elucidate the cytotoxic mechanism of UA. Implanted mouse hepatoma H22 was used to evaluate the growth inhibitory effect of UA in vivo.


RESULTS
UA could significantly inhibit the proliferation of HepG2 and its drug-resistance strain, R-HepG2 cells, but had no inhibitory effect on primarily cultured normal mouse hepatocytes whereas all the six derivatives of UA could not inhibit the growth of all tested cell lines. Further study on mechanism demonstrated that apoptosis and G0/G1 arrest were involved in the cytotoxicity and cleavage of poly-(ADP-ribose)-polymerase (PARP). Downregulation of cyclooxygenase-2 (COX-2) protein and upregulation of heat shock protein (HSP) 105 mRNA correlated to the apoptosis of HepG2 cells treated with UA. In addition, UA also could inhibit the growth of H22 hepatoma in vivo.


CONCLUSIONS
UA is a promising anti-tumor agent, but further work needs to be done to improve its solubility.
Tian
Ze
Z
Department of Pharmacology, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100094, China. zetian603@hotmail.com
Lin
Geng
G
Zheng
Rui-Xia
RX
Huang
Feng
F
Yang
Meng-Su
MS
Xiao
Pei-Gen
PG
D027983:Aralia / Q000737:chemistry*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D014315:Triterpenes / Q000302:isolation & purification / Q000627:therapeutic use*; D000097245:Ursolic Acid
D010936:Plant Extracts; D014315:Triterpenes; D000097245:Ursolic Acid