Ursolic acid (3-hydroxy-urs-12-en-28-oic acid) is a pentacyclic triterpenoid derived from leaves, berries, fruits, and flowers of medicinal plants, such as Rosemarinus officinalis. Ursolic acid has been shown to inhibit tumorigenesis, tumor promotion, and suppress angiogenesis. In our present study, we found that ursolic acid decreased cell proliferation rate and induce apoptosis in human breast cancer cell line, MDA-MB-231. When we checked the expression levels of proteins associated with apoptosis signal by using immunoblotting, we found that ursolic acid induces various apoptotic molecules related to either extrinsic or intrinsic apoptosis signal pathway in MDA-MB-231 cells. In our study, we found that ursolic acid induced the appearance of Fas receptor and cleavage of caspase-8, -3 and PARP. We also found that ursolic acid induced Bax up-regulation and Bcl-2 down-regulation and release of cytochrome C to the cytosol from mitochondria. Moreover, ursolic acid cleaved caspase-9 and decreased mitochondrial membrane potential (ΔΨm) as shown with JC-1 staining. These data indicate that ursolic acid induce apoptosis through both mitochondrial death pathway and extrinsic death receptor dependent pathway in MDA-MB-231 cells. Our data clearly indicate that ursolic acid could be used as a potential anticancer drug for breast cancer.

Inhalation of particulate matter aggravates respiratory symptoms in patients with chronic airway diseases, but the mechanisms underlying this response remain poorly understood. We used a proteomics approach to examine this phenomenon. Treatment of epithelial cells with BSAcoated titanium dioxide (TiO 2 ) particles altered 20 protein spots on the two-dimensional gel, and these were then analyzed by nano-LC-MS/MS. These proteins included defense-related, cell-activating, and cytoskeletal proteins implicated in the response to oxidative stress. The proteins were classified into four groups according to the time course of their expression patterns. For validation, RT-PCR was performed on extracts of in vitro TiO 2 -treated cells, and lung issues from TiO 2 -treated rats were analyzed by immunohistochemical staining and enzyme immunoassay. TiO 2 treatment was found to increase the amount of mRNA for macrophage migration-inhibitory factor (MIF). MIF was expressed primarily in epithelium and was elevated in lung tissues and bronchoalveolar lavage fluids of TiO 2 -treated rats as compared with shamtreated rats. Carbon black and diesel exhaust particles also induced expression of MIF protein in the epithelial cells.