Oleanolic acid isolated from Oldenlandia diffusa exhibits a unique growth inhibitory effect against ras-transformed fibroblasts

Abstract

Aims Oldenlandia diffusa (Willd.) Roxb. ( O. diffusa) is a commonly used traditional Chinese medicine for treating cancer. Its pharmacological activities and anti-cancer effects have been the focus of intense research in recent years. In the present study, we aim to investigate whether the five major compounds from O. diffusa possess a unique inhibitory activity against ras-transformed cells in a well-established cell model. Main methods The anti-cancer effects of O. diffusa were assessed in a co-culture system containing normal and transformed Rat 6 (R6) fibroblasts. In addition, a transwell assay was used to examine the interaction between the drugs and the co-cultivated cells. Key findings Our data showed that among the samples tested, oleanolic acid (OA), but not the structural isomer ursolic acid (UA), inhibits the growth of ras oncogene-transformed R6 cells at a dosage that is not toxic to the co-cultivated normal fibroblasts. A significant inhibitory effect was also observed in the transwell experiments, indicating that the mode of action for OA-mediated growth inhibition of transformed cells does not require direct cell-to-cell contact between normal and ras-transformed cells. Data obtained from experiments conducted with the conditioned medium that was collected from normal R6 cells treated with OA also suggest that OA might cause normal cells to secrete inhibitory factor(s) against the transformed cells. The enhanced ability of OA to cause cytotoxicity in transformed cells in the presence of normal fibroblasts is also observed with the human hepatocellular carcinoma cell line, SMMC-7721. Significance The present study demonstrates that OA may possess both cancer chemotherapeutic and chemopreventive activities. Thus, it may have great potential for clinical application as a novel anti-cancer drug.