Effects of ursolic acid and oleanolic acid on human colon carcinoma cell line HCT15.
OBJECTIVE
Ursolic acid (UA) and oleanolic acid (OA) are triperpene acids having a similar chemical structure and are distributed wildly in plants all over the world. In recent years, it was found that they had marked anti-tumor effects. There is little literature currently available regarding their effects on colon carcinoma cells. The present study was designed to investigate their inhibitory effects on human colon carcinoma cell line HCT15.


METHODS
HCT15 cells were cultured with different drugs. The treated cells were stained with hematoxylin-eosin and their morphologic changes observed under a light microscope. The cytotoxicity of these drugs was evaluated by tetrazolium dye assay. Cell cycle analysis was performed by flow cytometry (FCM). Data were expressed as means +/-SEM and Analysis of variance and Student' t-test for individual comparisons.


RESULTS
Twenty-four to 72 h after UA or OA 60 micromol/L treatment, the numbers of dead cells and cell fragments were increased and most cells were dead at the 72nd hour. The cytotoxicity of UA was stronger than that of OA. Seventy-eight hours after 30 micromol/L of UA or OA treatment, a number of cells were degenerated, but cell fragments were rarely seen. The IC(50) values for UA and OA were 30 and 60 micromol/L, respectively. Proliferation assay showed that proliferation of UA and OA-treated cells was slightly increased at 24h and significantly decreased at 48 h and 60 h, whereas untreated control cells maintained an exponential growth curve. Cell cycle analysis by FCM showed HCT15 cells treated with UA 30 and OA 60 for 36 h and 72 h gradually accumulated in G(0)/G(1) phase (both drugs P<0.05 for 72 h), with a concomitant decrease of cell populations in S phase (both drugs P<0.01 for 72 h) and no detectable apoptotic fraction.


CONCLUSIONS
UA and OA have significant anti-tumor activity. The effect of UA is stronger than that of OA. The possible mechanism of action is that both drugs have an inhibitory effect on tumor cell proliferation through cell-cycle arrest.
Li
Jie
J
Department of Oncology, Cancer Center, Xin Hua Hospital, Shanghai Second Medical University, Shanghai 200092, China. ljee@citiz.net
Guo
Wei-Jian
WJ
Yang
Qing-Yao
QY
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D009828:Oleanolic Acid / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000097245:Ursolic Acid
D000972:Antineoplastic Agents, Phytogenic; D009828:Oleanolic Acid; D014315:Triterpenes; D000097245:Ursolic Acid