Tetrabromobisphenol A (TBBPA) is the most widely used brominated flame retardants (BFRs). It has been detected in various environment media and has been approved to be high toxic to aquatic organisms. However, the exposure levels of TBBPA in the main watersheds in China have not been investigated sufficiently. In this study TBBPA concentrations in water, sediment and tissues of four fish species from Lake Chaohu were determined. Spatial and temporal distribution patterns of TBBPA in water and sediment, and the relationship among TBBPA concentrations in fish tissues and fish size were analyzed. The results showed that the maximum TBBPA concentration in sediment was 518 ng/g in March 2008. It is almost the highest value than those ever reported anywhere in the world. In lake water, TBBPA level reached the maximum value of 4.87 μg/L in July. Tissue distributions of TBBPA in four fish species were similar, and the mean concentrations in the fish were in the range of 28.5-39.4 ng/g, much higher than those reported in Japan, Europe, and the United States. The maximum concentrations of TBBPA were found in kidneys where TBBPA concentration was positively correlated with fish size of Cyprinus carpio. Results demonstrated a widespread distribution of TBBPA in Lake Chaohu. The source was mainly inflow rivers near the cities. The distribution coefficient among water, fish, and sediment was 1:28:117. This indicated that sediment was the main repository for TBBPA within Lake Chaohu. Furthermore, TBBPA may pose a potential ecological risk in the lake during summer.
Lung cancer is the leading cause of cancer death worldwide. Recently, two plant-derived drugs triptolide (TP) and hydroxycamptothecin (HCPT) both have shown broad-spectrum anticancer activities. Our previous study documented that combination treatment with these two drugs acted more effectively than mono-therapy, however, the molecular basis underlying the synergistic cytotoxicity remains poorly understood. In this study, we aimed to clarify the molecular mechanism of TP/HCPT anticancer effect in A549 lung adenocarcinoma cells, by investigating the involvement of phosphatase 2A (PP2A) and PP2A-regulated mitogen-activated protein kinases (MAPKs) and Akt signaling pathways. The results showed that TP and HCPT synergistically exerted cytotoxicity in the growth of A549 cells. Combinatorial TP/HCPT treatment significantly enhanced the activation of caspase-3 and -9, Bax/Bcl-2 ratio, release of cytochrome c from mitochondrial and subsequent apoptosis. While the Akt survival pathway was inhibited, ERK and p38 MAPKs were dramatically activated. Furthermore, the activity of PP2A was significantly augmented. Regulation of p38, ERK and Akt by PP2A was demonstrated, by using a specific PP2A inhibitor okadaic acid (OA). Finally, pharmacological inhibitors OA, SB203580, SP600125 and PD98059 confirm the role of PP2A and its substrates ERK, p38 MAPK and Akt in mediating TP/HCPT-induced apoptosis. Taken together, this study provides the first evidence for a synergistic TP/HCPT anti-cancer activity in A549 cells and also supports a critical role of PP2A and PP2A-regulated signaling pathways, providing new insight into the mode of action of TP/HCPT in cancer therapy.
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