extract of Perilla stem inhibits Src homology phosphatase-1 [SHP]-1 and influences insulin signaling

Protein tyrosine phosphatases [PTPs] are enzymes that catalyze protein tyrosine dephosphorylation of which Src homology phosphatase-1 [SHP-1] is one of the best-validated, a widely distributed intracellular tyrosine phosphatase that contains two SH2 domains. Down regulation of SHP-1 tyrosine phosphatases was significantly increased sensitivity to insulin in insulin signaling pathway. Through in vitro enzymatic reaction kinetics experiment, we found that the extract of Perilla stem was a potential inhibitor to [delta]SHP-1, the catalytic domain of SHP-1 protein tyrosine phosphatase, and its IC[50] was 4ug/ml, and was more sensitive towards SHP-1than other PTPs, which indicated that SHP-1 might be a target of the extract of Perilla stem. It can strengthened the level of tyrosine phosphorylation of insulin receptor [IR] and extracellular signal-regulated protein kinase [ERK] in HepG2 cells, and then activated the insulin signaling pathway through inhibiting the protein phosphorylation of SHP-1. These results demonstrated that the extract of Perilla stem could play an important role for diabetes treatment through inhibiting the level of SHP-1 in insulin signaling pathway

Assessment of the estrogenicity of endosulfan and other chemicals with the in vitro proliferation of human breast cancer cell / 浙江大学学报·医学版

OBJECTIVE: To develop a rapid screening method for xenoestrogens and to screen the estrogenicity of some environmental chemicals. METHODS: The E-SCREEN test was developed based on proliferation of human breast cancer cells (MCF-7), and the estrogenicity of diethylstilbestrol, 4-hydrotamoxifen and endosulfan was assessed. RESULTS: The E-SCREEN detected estradiol at very low concentration as 1x10(-13) mol/L. It was found that diethylstilbestrol was a full agonist of estrogen receptor, endosulfan was a partial agonist, while 4 hydrotamoxifen lacked estrogenic effects at this assay. CONCLUSION: The E-SCREEN test is sensitive, rapid, easy to perform and, therefore, suitable for large scale screening for estrogenicity of environmental chemicals.