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.

Chronic exposure to quinalphos shows biochemical changes and genotoxicty in erythrocytes of silver barb, Barbonymus gonionotus.

An in vivo study was carried out on the freshwater fish Barbonymus gonionotus to evaluate the genotoxic effects of the organophosphate quinalphos. The fish were exposed to sub-lethal doses of quinalphos (0%, 10%, 25%, and 50% of LC50) for a period of 30 days. Analysis of biochemical characteristics (protein and lipid contents of different organs), nuclear abnormalities of erythrocytes (NAE) and morphological abnormalities of erythrocytes (MAE) were performed on peripheral erythrocytes sampled at post-treatment intervals of 0 and 30 days. The biochemical results revealed a significant dose-dependent decline in protein and lipid contents and increase in the frequencies of NAE as well as MAE. Our findings also confirmed that the morphological deformations of erythrocytes in addition to NAE on fish erythrocytes in vivo are effective tools in determining the potential genotoxicity of organophosphates.