Conventional chemotherapy is commonly used in the treatment of metastasis cancers although it exhibits cytotoxic effects on normal cells. Agents that target metastatic components have high selectivity against malignant cells. Also, the combined treatment of conventional chemotherapy and anti-metastatic agents can be used to increase the therapeutic efficacy. Many novel agents from natural compounds that have potential in metastatic cancer therapy without displaying cytotoxic effects are being explored. Here, we report an investigation of curcusone B, a diterpene isolated from Jatropha curcas Linn., a herbal plant that has been used in traditional folk medicine of Northeastern Thailand. We found that this compound exhibited anti-invasive effect on KKU-100 cells by inhibiting cell motility and matrix metalloproteinase secretion. Cell motility is a dynamic process of cytoskeleton reorganization consisting of cell protrusion, creation of new attachment, detachment of cell rear and cell contraction. Many signaling pathways are involved in regulation of cell movement. In this study, we investigated the effects of curcusone B on cytoskeleton and signal transduction pathways that might be involved. The changes of filamentous actin pattern were visualized by fluorescent staining. The reduction of the phosphorylation level of myosin regulatory light chain was detected by western blotting. However, cofilin phosphorylation was not effected by curcusone B. The effect of curcusone B on other signaling molecules and cytoskeletal proteins will be further investigated.

[Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006]