hepatoma activity and mechanism of ursolic acid and its derivatives isolated from Aralia decaisneana . World J Gastroenterol 2006; 12(6): 874-879 http://www.wjgnet.com/1007-9327/12/874.asp
INTRODUCTIONHepatocellular carcinoma is one of the most common malignant neoplasms worldwide and one of the leading causes of malignancy-related death in China [1,2] . Its therapy in clinic is still a big challenge.Ursolic acid (UA) is a versatile compound, which possesses anti-cancer [3,4] , anti-inflammatory [5,6] , anti-HIV [7] and immunomodulatory effects [8] . There is a growing interest in the anti-tumor activities of UA. UA could act on almost all steps in the whole cancer process: initiation, promotion, progression, and metastasis. Multiple lines of evidence indicate that UA is a promising chemo-preventive agent both in vivo and in vitro. UA could inhibit Epstein-Barr virus activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells and two-stage mouse skin tumor promotion [9,10] . The mechanism involved might associate with the inhibition of AP-1-mediated induction of COX-2 by disrupting PKC signal transduction pathway [11] . UA could inhibit the proliferation of various cancerous cell lines by inhibiting DNA polymerase and topoisomerase [12] , inducing apoptosis through proteolytic activation of caspase-3 and/ or other similar caspases [3] . It was also reported that UA has anti-invasion and anti-metastasis activity by inhibiting nuclear factor-kappa B (NF-κB) activation, down-regulating COX-2 and matrix metalloproteinase 9 [13] . Besides its cytotoxicity to hepatoma, it was reported that UA can exert its hepatoprotective action in mice and rats [14][15][16] . The reason for the phenomenon is worth studying. Moreover, the growth inhibitory activity of UA on hepatocellular carcinoma in vivo is still unknown.In the present study, UA and its six derivatives isolated from the bark of Aralia decaisneana were used to treat rheumatism, lumbago, hepatitis, nephritis, and diabetes mellitus in Chinese folk medicine. The cytotoxicity of these UA compounds to HepG2, its drug-resistance strain R-HepG2 and primarily cultured normal mouse and rat hepatocytes were examined in order to find their antihepatoma efficiency on both parental and drug-resistant hepatocellular carcinoma as well as their low toxicity.
LIVER CANCER
Anti-hepatoma activity and mechanism of ursolic acid and its derivatives isolated from Aralia decaisneana
Abstract
AIM: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 signifi...