cyclin-d1 and 25-methoxydammarane-3-12-20-triol

1. The Wnt/beta-catenin pathway plays a critical role in carcinogenesis and so agents that target Wnt/beta-catenin may have potential in cancer prevention and therapy. The aim of the present study was to evaluate the anticancer activity of the novel natural product dammarane-type triterpene sapogenin (20(S)-25-OCH3-PPD; PPD25) isolated from the leaves of Panax notoginseng. 2. The anticancer activity of PPD25 was evaluated in three colon cancer cell lines and in one lung cancer cell line. The effects of PPD25 to inhibit proliferation and to induce apoptosis were evaluated. In addition, the potential mechanisms underlying the effects of PPD25 were investigated. 3. It was found that the addition of 5 or 25 micromol/L PPD25 to the culture medium significantly inhibited cell proliferation and induced apoptosis in all four cancer cell lines. Mechanistic studies revealed that PPD25 significantly reduced the expression of beta-catenin, a key mediator in the Wnt pathway, as well as transcriptional targets of beta-catenin, namely c-myc, cyclin D1, cdk4 and T cell factor (TCF)-4. In addition, beta-catenin/TCF transcriptional activity was significantly suppressed by PPD25. 4. The data demonstrate that the PPD25 exerts its anticancer effect by targetting beta-catenin signalling, suggesting that PPD25 may have potential as a chemotherapeutic and/or chemopreventive agent for colon and lung cancer.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; beta Catenin; Cell Line, Tumor; Cell Proliferation; Cyclin D1; Cyclin-Dependent Kinase 4; Drug Delivery Systems; Drug Screening Assays, Antitumor; Drugs, Chinese Herbal; Humans; Proto-Oncogene Proteins c-myc; Signal Transduction; TCF Transcription Factors; Transcription Factor 7-Like 2 Protein; Transcriptional Activation; Triterpenes; Wnt Proteins