PTU, a novel ureido-fatty acid, inhibits MDA-MB-231 cell invasion and dissemination by modulating Wnt5a secretion and cytoskeletal signaling.

Migration and invasion promote tumor cell metastasis, which is the leading cause of cancer death. At present there are no effective treatments. Epidemiological studies have suggested that ω-3 polyunsaturated fatty acids (PUFA) may decrease cancer aggressiveness. In recent studies epoxide metabolites of ω-3 PUFA exhibited anti-cancer activity, although increased in vivo stability is required to develop useful drugs. Here we synthesized novel stabilized ureido-fatty acid ω-3 epoxide isosteres and found that one analogue - p-tolyl-ureidopalmitic acid (PTU) - inhibited migration and invasion by MDA-MB-231 breast cancer cells in vitro and in vivo in xenografted nu/nu mice. From proteomics analysis of PTU-treated cells major regulated pathways were linked to the actin cytoskeleton and actin-based motility. The principal finding was that PTU impaired the formation of actin protrusions by decreasing the secretion of Wnt5a, which dysregulated the Wnt/planar cell polarity (PCP) pathway and actin cytoskeletal dynamics. Exogenous Wnt5a restored invasion and Wnt/PCP signalling in PTU-treated cells. PTU is the prototype of a novel class of agents that selectively dysregulate the Wnt/PCP pathway by inhibiting Wnt5a secretion and actin dynamics to impair MDA-MB-231 cell migration and invasion.

A laboratory method for concurrently determining diffusion migration parameters and water saturation effects of thoron in uranium tailings.

Environmental humidity has a significanteffect on changes in free 220Rn (thoron) production rate and effective diffusion coefficient of 220Rn in uranium tailings. To understand such changes, a closed cavity containing porous 220Rn media with finite thickness was studied. Based on the 220Rn diffusion migration theory in porous media with finite thickness, a model for calculating the uniform 220Rn activity concentration in a closed container with porous media of finite thickness was established. A laboratory method for concurrently determining free 220Rn production rate and effective diffusion coefficient of 220Rn was proposed and a corresponding experimental setup was made. With samples taken from a uranium tailing impoundment in southern China, water content, free 220Rn production rate, and effective diffusion coefficient of 220Rn in uranium tailings were determined under certain environmental temperature and humidity conditions. Results show that: (1) The method and experimental setup presented in this study can simultaneously determine free 220Rn production rate and effective diffusion coefficient of 220Rn in porous media such as uranium tailing; (2) The free 220Rn production rate in uranium tailings increases linearly with water saturation. Effective diffusion coefficient of 220Rn, on the other hand, decreases exponentially with the increase in water saturation.