Indole-3-acetate induces apoptosis and stimulates phosphorylation of p65NF-κB in 143B and HOS osteosarcoma cells

Purpose: To investigate the effect of indole-3-acetate (IAA) on the proliferation of 143B and HOS osteosarcoma cells, and its mechanism of action.Methods: Indole-3-acetate (IAA)-induced changes in cell proliferation and apoptosis were investigated using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. The effects of IAA on expressions of mRNAs for phosphatase and tensin homolog (PTEN), fas ligand (FasL), and fas receptor (FasR) were evaluated using western blot assay.Results: Early apoptosis in 143B cell cultures due to addition of IAA (5 μM) was 34.67 %, relative to 2.82 % in untreated cultures. In HOS cells, IAA caused 39.21 % apoptosis, relative to 3.53 % apoptosis in control. The addition of IAA to the cell cultures significantly enhanced the expressions of mRNAs for PTEN, FasL and FasR, compared to untreated cells (p < 0.05). Western blot analysis showed that IAA caused a significant decrease in the level of IκBα expression in both cell lines (p < 0.05). In 143B and HOS cells, treatment with IAA led to accumulation of higher levels of NF-κB in the nucleus than in the cytosol. The levels of cytosolic NF-κB, and nuclear lamin B1 in IAA-treated cells were lower than the corresponding levels in untreated cells.Conclusion: These results indicate that IAA inhibits proliferation, and induces apoptosis in 143B and HOS cells via activation of NF-κB, and its translocation to the nucleus. Therefore, IAA may be a useful drug target in the treatment of osteosarcoma.Keywords: Indole-3-acetate, Phosphatase, Fas receptor, Translocation, Proliferation, Tumoricidal activit

17β-Estradiol Enhances Breast Cancer Cell Motility and Invasion via Extra-Nuclear Activation of Actin-Binding Protein Ezrin

Estrogen promotes breast cancer metastasis. However, the detailed mechanism remains largely unknown. The actin binding protein ezrin is a key component in tumor metastasis and its over-expression is positively correlated to the poor outcome of breast cancer. In this study, we investigate the effects of 17β-estradiol (E2) on the activation of ezrin and its role in estrogen-dependent breast cancer cell movement. In T47-D breast cancer cells, E2 rapidly enhances ezrin phosphorylation at Thr567 in a time- and concentration-dependent manner. The signalling cascade implicated in this action involves estrogen receptor (ER) interaction with the non-receptor tyrosine kinase c-Src, which activates the phosphatidylinositol-3 kinase/Akt pathway and the small GTPase RhoA/Rho-associated kinase (ROCK-2) complex. E2 enhances the horizontal cell migration and invasion of T47-D breast cancer cells in three-dimensional matrices, which is reversed by transfection of cells with specific ezrin siRNAs. In conclusion, E2 promotes breast cancer cell movement and invasion by the activation of ezrin. These results provide novel insights into the effects of estrogen on breast cancer progression and highlight potential targets to treat endocrine-sensitive breast cancers

Dechlorane plus (DP) in indoor and outdoor air of an urban city in South China: Implications for sources and human inhalation exposure

Dechlorane Plus (DP) is a chemical of emerging concern due to the restrictions on brominated flame retardant formulations. However, very little information is known about the occurrence of DP in indoor and outdoor air and its associated health risk to the exposed human population. In this study, we examined the concentrations and isomer profiles of DP in archived air samples collected from 14 homes, 6 offices, and 10 public microenvironments in Guangzhou, China in 2004-2005. The average (median) value of atmospheric sigma DP (sum of anti-DP and syn-DP) concentration in the three indoor air was 5.73 +/- 5.33 (3.62) for offices, 8.08 +/- 5.17 (6.87) for homes, and 57.27 +/- 83.08 (32.58) pg/m(3) for public microenvironments, respectively. sigma DP concentration was significantly higher in the public microenvironments than those in homes and offices. The arithmetic mean and median concentrations of sigma DP in outdoor air were 36.00 and 28.76pg/m(3), respectively. Spatially and temporally consistent indoor and outdoor samples comparison suggested that outdoor air might be a relevant source of DP for indoor air. Average anti-DP fractional abundance (f(anti) = 0.65 +/- 0.04) in all outdoor samples was similar to those reported in other studies and indistinguishable from that of the commercial mixture (f(anti) = 0.65). In contrast, a relatively large variation of f(anti) values was found in the indoor samples, suggesting a complex degradation process of DP existing in these microenvironments. The calculated average daily doses of sigma DP were in the range of 0.38-2.21ng/day for people intake through air inhalation, which was in the same order of magnitude compared with other exposure pathways for the general publics

On the Degree of Boolean Functions as Polynomials over Zm

Polynomial representations of Boolean functions over various rings such as ? and ?_m have been studied since Minsky and Papert (1969). From then on, they have been employed in a large variety of areas including communication complexity, circuit complexity, learning theory, coding theory and so on. For any integer m ? 2, each Boolean function has a unique multilinear polynomial representation over ring ?_m. The degree of such polynomial is called modulo-m degree, denoted as deg_m(?). In this paper, we investigate the lower bound of modulo-m degree of Boolean functions. When m = p^k (k ? 1) for some prime p, we give a tight lower bound deg_m(f) ? k(p-1) for any non-degenerate function f:{0,1}? ? {0,1}, provided that n is sufficient large. When m contains two different prime factors p and q, we give a nearly optimal lower bound for any symmetric function f:{0,1}? ? {0,1} that deg_m(f) ? n/{2+1/(p-1)+1/(q-1)}

Plumbagin Triggers ER Stress-Mediated Apoptosis in Prostate Cancer Cells via Induction of ROS

Background/Aims: Prostate cancer (PCa) is the second most frequently diagnosed cancer in men worldwide. Currently available therapies for hormone-refractory PCa are only marginally effective. Plumbagin (PLB), a natural naphthoquinone isolated from the traditional folk medicine Plumbago zeylanica, is known to selectively kill tumor cells. Nevertheless, antitumor mechanisms initiated by PLB in cancer cells have not been fully defined. Methods: MTT assay was used to evaluate the effect of PLB on the viability of cancer cells. Cell apoptosis and reactive oxygen species (ROS) production were determined by flow cytometry. Protein expression was detected by western blotting. In vivo anti-tumor effect was measured by using tumor xenoqraft model in nude mice. Results: In the present study, we found that PLB decreases cancer cell growth and induces apoptosis in DU145 and PC-3 cells. In addition, by increasing intracellular ROS levels, PLB induced a lethal endoplasmic reticulum stress response in PCa cells. Importantly, blockage of ROS production significantly reversed PLB-induced ER stress activation and cell apoptosis. In vivo, we found that PLB inhibits the growth of PCa xenografts without exhibiting toxicity Treatment of mice bearing human PCa xenografts with PLB was also associated with induction of ER stress activation. Conclusion: Inducing ER stress by PLB thus discloses a previously unrecognized mechanism underlying the biological activity of PLB and provides an in-depth insight into the action of PLB in the treatment of hormone-refractory PCa

Polybrominated diphenyl ethers and polychlorinated biphenyls in mangrove sediments of Shantou, China: Occurrence, profiles, depth-distribution, and risk assessment

Surface and columnar sediments were collected from four mangrove Wetlands in Shantou coastal areas of South China to investigate the level, distribution, possible sources and ecotoxicological risks of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs). Total concentration of 14 PBDEs (Sigma 14PBDEs) and 41 PCBs (Sigma(41)PCBs) varied from 0.61 to 180 ng/g and 42-636 pg/g dry weight (dw) in surface sediments, respectively. The concentration of PBDEs was much higher than that of PCBs. Compared with other mangrove Wetlands around the world, PCBs levels in the studied area were relatively low, while the concentrations of PBDE were at higher level. Decabromodiphenyl ether (BDE-209) was the predominant PBDEs homologue in all sediment samples, indicating the extensive use of deca-BDE in this area. Penta-CBs and hexa-CBs were the main homologues of PCBs. Spatial variations showed that the concentration of PBDEs might be mainly affected by anthropogenic activities in specific sites of this region, whereas dry and wet deposition might be an important input source of PCBs in this area. Although accurate sediment chronology was not available, higher concentrations of PBDEs and PCBs were still found in some deeper sediment layers, suggesting that new input quantity tends to decrease with the increase of control. Risk assessment showed that penta-BDEs and deca-BDE may have potential negative ecological effects on the ecological of Shantou mangrove sediments, while the effects of PCBs can be neglected