Anti-hepatoma activity and mechanism of ursolic acid and its derivatives isolated from Aralia decaisneana.
Ключевые слова
абстрактный
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.
