Celecoxib inhibits cell growth and modulates the expression of matrix metalloproteinases in human osteosarcoma MG-63 cell line.

OBJECTIVE: The goal of this study was to determine the effect of celecoxib, a selective COX-2 inhibitor, on the growth inhibition of osteosarcoma and its potential anticancer mechanisms. MATERIALS AND METHODS: Human osteosarcoma cell line MG-63 was used as a model. The inhibitory effect of celecoxib on cell proliferation was assessed by MTT assay. Flow cytometric analysis was used to detect the effects of celecoxib on cell cycle and apoptosis. Western blot analysis was used to detect the protein expression of RECK, matrix metalloproteinase (MMP)-2 and MMP-9 in celecoxib-treated MG-63 cells. RESULTS: MTT assays showed that at a range of concentrations (0-80 µg/ml), celecoxib significantly inhibited the MG-63 cell proliferation in a time- and concentration-dependent manner. The half maximal inhibitory concentration (IC50) of celecoxib was 47.5 µg/ml for 24 h-treatment and 19.2 µg/ml for 48 h-treatment. Flow cytometric analysis demonstrated that treatment with 20 µg/ml celecoxib led to a significant cell cycle arrest at S-phase and an enhancement of apoptosis induction in MG-63 cells at 24 or 48h. Moreover, compared with 24 h-treatment, 48 h-treatment induced more S-phase arrest and apoptosis in MG-63 cells. Western blot analyses revealed that the expression of MMP-2 and MMP-9 was markedly down-regulated but RECK, an inhibitor of MMPs, was markedly up-regulated in MG-63 cells exposed to 20 µg/ml celecoxib for 24 or 48h. Furthermore, the effects of celecoxib on the expression of these molecules were more evident with the increase of treatment time. CONCLUSIONS: Celecoxib inhibits the MG-63 cells proliferation through S-phase arrest and apoptosis induction. Celecoxib-induced down-regulation of MMP-2 and MMP-9 and up-regulation of RECK may contribute to the apoptosis induction and an alteration in local tumor microenvironment. These findings suggest that celecoxib may exert at least in part of its anticancer effects via up-regulation of RECK to inhibit the expression of MMP-2 and MMP-9.

Environmental fate and effects of dicamba: a Canadian perspective.

Literature on the environmental fate and effects of the benzoic acid herbicide dicamba was reviewed to provide a scientific basis to derive Canadian Water Quality Guidelines. Included in the review was information on the uses and production of dicamba, its physical and chemical properties, environmental monitoring data in Canadian surface water and groundwater, soils, sediments, and biota, and its environmental degradation, persistence, and fate. Through monitoring, dicamba has been detected in less than 8% of surface-water samples to a maximum concentration of 13 micrograms.L-1, while 2% of groundwater samples were positive up to 517 micrograms.L-1. Only one study that analyzed sediments (with no detections) and no field studies that investigated residues in biota were found. Microbial degradation is the most important process governing the dissipation of dicamba in aquatic and soil environments. Photolysis, hydrolysis, volatilization, adsorption to sediment, and bioconcentration are not expected to be significant removal processes, based on limited environmental fate data. The half-life of dicamba in water is < 7 d, although residues have been detected in surface-water supplies in Alberta more than 6 mon after application. The literature reports the half-life in soils ranges from 4 to 555 d; however, < 12 wk would be typical under Canadian conditions. High moisture and temperature, and other conditions that favor microbial degradation, would likely reduce the half-life to < 4 wk. The principal soil and plant metabolite is 3,6-dichlorosalicylic acid, with minor amounts of 2,5-dihydroxy-3,6-dichlorobenzoic acid and 5-hydroxydicamba found. Dicamba is highly mobile in soil, and significant leaching is possible; its water solubility is 6.5 g.L-1 (25 degrees C) and it has a log octanol-water partition coefficient of 0.477. Acute and chronic toxicological studies for all nontarget plants and animals were also reviewed. The major groups of organisms for which toxicological data were collected were freshwater fish, invertebrates and plants, tame hays and cereals, legumes, and other crops, and livestock poultry and mammals. The acute toxicity (< or = 96-hr LC50) to freshwater fish ranged from 28 to 516 mg.L-1, whereas that for invertebrates ranged from 3.9 to > 100 mg.L-1. No chronic data were found for either of these groups. The chronic EC50 to 14 freshwater algae, based on growth inhibition, ranged from 100 to > 10,000 micrograms.L-1. No studies on freshwater macrophytes or any marine organisms were found. Agricultural crops exhibited varying toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

A laser-Compton scattering prototype experiment at 100 MeV linac of Shanghai Institute of Applied Physics.

As a prototype of the Shanghai Laser Electron Gamma Source in the Shanghai Synchrotron Radiation Facility, an x-ray source based on laser-Compton scattering (LCS) has been installed at the terminal of the 100 MeV linac of the Shanghai Institute of Applied Physics. LCS x-rays are generated by interactions between Q-switched Nd:yttrium aluminum garnet laser pulses [with wavelength of 1064 nm and pulse width of 21 ns (full width at half maximum)] and electron bunches [with energy of 108 MeV and pulse width of 0.95 ns (rms)] at an angle of 42 degrees between laser and electron beam. In order to measure the energy spectrum of LCS x-rays, a Si(Li) detector along the electron beam line axis is positioned at 9.8 m away from a LCS chamber. After background subtraction, the LCS x-ray spectrum with the peak energy of 29.1+/-4.4|(stat)+/-2.1|(syst) keV and the peak width (rms) of 7.8+/-2.8|(stat)+/-0.4|(syst) keV is observed. Normally the 100 MeV linac operates with the electron macropulse charge of 1.0 nC/pulse, and the electron and laser collision repetition rate of 20 Hz. Therefore, the total LCS x-ray flux of (5.2+/-2.0) x 10(2) Hz can be achieved.