Genistein-Inhibited Cancer Stem Cell-Like Properties and Reduced Chemoresistance of Gastric Cancer

Key Projects of Fujian Province Technology [2010D026]; China Postdoctoral Science Foundation [2012M521279]; Medical innovations Topic in Fujian Province [2012-CXB-9]; projects of Xiamen scientific and technological plan [3502Z20124018, 3502Z20134011]Genistein, the predominant isoflavone found in soy products, has exerted its anticarcinogenic effect in many different tumor types in vitro and in vivo. Accumulating evidence in recent years has strongly indicated the existence of cancer stem cells in gastric cancer. Here, we showed that low doses of genistein (15 M), extracted from Millettia nitida Benth var hirsutissima Z Wei, inhibit tumor cell self-renewal in two types of gastric cancer cells by colony formation assay and tumor sphere formation assay. Treatment of gastric cancer cells with genistein reduced its chemoresistance to 5-Fu (fluorouracil) and ciplatin. Further results indicated that the reduced chemoresistance may be associated with the inhibition of ABCG2 expression and ERK 1/2 activity. Furthermore, genistein reduced tumor mass in the xenograft model. Together, genistein inhibited gastric cancer stem cell-like properties and reduced its chemoresistance. Our results provide a further rationale and experimental basis for using the genistein to improve treatment of patients with gastric cancer

A male sterility-associated cytotoxic protein ORF288 in Brassica juncea causes aborted pollen development

Cytoplasmic male sterility (CMS) is a widespread phenomenon in higher plants, and several studies have established that this maternally inherited defect is often associated with a mitochondrial mutant. Approximately 10 chimeric genes have been identified as being associated with corresponding CMS systems in the family Brassicaceae, but there is little direct evidence that these genes cause male sterility. In this study, a novel chimeric gene (named orf288) was found to be located downstream of the atp6 gene and co-transcribed with this gene in the hau CMS sterile line. Western blotting analysis showed that this predicted open reading frame (ORF) was translated in the mitochondria of male-sterile plants. Furthermore, the growth of Escherichia coli was significantly repressed in the presence of ORF288, which indicated that this protein is toxic to the E. coli host cells. To confirm further the function of orf288 in male sterility, the gene was fused to a mitochondrial-targeting pre-sequence under the control of the Arabidopsis APETALA3 promoter and introduced into Arabidopsis thaliana. Almost 80% of transgenic plants with orf288 failed to develop anthers. It was also found that the independent expression of orf288 caused male sterility in transgenic plants, even without the transit pre-sequence. Furthermore, transient expression of orf288 and green fluorescent protein (GFP) as a fused protein in A. thaliana protoplasts showed that ORF288 was able to anchor to mitochondria even without the external mitochondrial-targeting peptide. These observations provide important evidence that orf288 is responsible for the male sterility of hau CMS in Brassica juncea

Genistein-Inhibited Cancer Stem Cell-Like Properties and Reduced Chemoresistance of Gastric Cancer

Genistein, the predominant isoflavone found in soy products, has exerted its anticarcinogenic effect in many different tumor types in vitro and in vivo. Accumulating evidence in recent years has strongly indicated the existence of cancer stem cells in gastric cancer. Here, we showed that low doses of genistein (15 µM), extracted from Millettia nitida Benth var hirsutissima Z Wei, inhibit tumor cell self-renewal in two types of gastric cancer cells by colony formation assay and tumor sphere formation assay. Treatment of gastric cancer cells with genistein reduced its chemoresistance to 5-Fu (fluorouracil) and ciplatin. Further results indicated that the reduced chemoresistance may be associated with the inhibition of ABCG2 expression and ERK 1/2 activity. Furthermore, genistein reduced tumor mass in the xenograft model. Together, genistein inhibited gastric cancer stem cell-like properties and reduced its chemoresistance. Our results provide a further rationale and experimental basis for using the genistein to improve treatment of patients with gastric cancer

An Ecologically Oriented Operation Strategy for a Multi-Reservoir System: A Case Study of the Middle and Lower Han River Basin, China

Constructing and operating a multi-reservoir system changes the natural flow regime of rivers, and thus imposes adverse impacts on riverine ecosystems. To balance human needs with ecosystem needs, this study proposes an ecologically oriented operation strategy for a multi-reservoir system that integrates environmental flow requirements into the joint operation of a multi-reservoir system in order to maintain different ecological functions throughout the river. This strategy is a combination of a regular optimal operation scheme and a series of real-time ecological operation schemes. During time periods when the incompatibilities between human water needs and ecosystem needs for environmental flows are relatively small, the regular optimal operation scheme is implemented in order to maximize multiple human water-use benefits under the constraints of a minimum water-release policy. During time periods when reservoir-induced hydrological alteration imposes significant negative impacts on the river’s key ecological functions, real-time ecological operation schemes are implemented in order to modify the outflow from reservoirs to meet the environmental flow requirements of these functions. The practical use of this strategy is demonstrated for the simulation operation of a large-scale multi-reservoir system which located in the middle and lower Han River Basin in China. The results indicate that the real-time ecological operation schemes ensure the environmental flow requirements of the river’s key ecological functions, and that adverse impacts on human water-use benefits can be compensated for by the regular optimal operation scheme. The ecologically oriented operation strategy for a multi-reservoir system that is proposed in this study enriches the theoretical application of the multi-reservoir system joint operation which considers environmental flow requirements. Keywords: Multi-reservoir system, Ecologically oriented operation, Environmental flow requirements, Han River Basi