Cytotoxicity of three cycloartane triterpenoids from Cimicifuga dahurica

Abstract 

We first investigated the cytotoxicity of three cycloartane triterpenoids isolated from the aerial part of C. dahurica. Their cytotoxic activity was investigated on several cancer cell lines including solid tumor (HepG2), blood tumor (HL-60), drug resistant tumor (R-HepG2) and primary cultured normal mouse and rat hepatocytes in order to find efficient anti-tumor agents against both parental and drug-resistant tumor with reduced toxicity. Evident cytotoxicity of these compounds on all tested neoplastic cell lines revealed that they are efficient on both drug-resistant tumor and parental tumor. Furthermore, they all showed relatively selective cytotoxicity on cancerous cells based on the higher IC₅₀ values of them on normal cells than that on tumor cells. Morphological observation and cell cycle analysis were employed to elucidate the cytotoxicity of the tested compounds. They brought out similar apoptotic morphological changes and G₂/M cell cycle arrest in HepG2, R-HepG2 and HL-60 cells. Moreover, they suppressed the expression of cdc2 and COX-2 protein. These results imply that the three compounds possess potential anti-tumor activities and they exert their cytotoxicity via apoptosis and G₂/M arrest. In addition, inhibition of cdc2 protein expression correlates with mechanism of G₂/M arrest.

Keywords: Cycloartane triterpenoids, Cytotoxicity, Apoptosis, Cell cycle, cdc 2, Cyclooxygenase-2