Background:Hypoxia-inducible factor 1 (HIF1) has been implicated in regulating many of the genes responsible for angiogenesis, erythropoiesis, glucose metabolism and cancer pathogenesis. In this study, we demonstrate that exposure of human breast cancer lines to 17β-oestradiol (E2) rapidly induced the expression of HIF-1α, the regulated subunit of HIF1, in normoxic condition. Hypoxia-inducible factor-1α is normally degraded in normoxia through ubiquitination-mediated proteolysis, whereas hypoxia modulates HIF-1α level by inhibiting ubiquitination-mediated degradation.Methods:Oestradiol-induced accumulation of HIF-1α in breast cancer lines was detected by western blot analysis and its promoter activity was measured by HIF1 reporter assay. Molecular signalling of oestradiol-mediated HIF-1α expression was studied using specific pharmacological inhibitors and small interference RNA by co-immunoprecipitation and western blotting analysis.Results:Oestradiol has been observed to rapidly activate the nongenomic signalling cascade leading to HIF-1α protein synthesis. The results define a signalling pathway in breast cancer cells whereby oestradiol induces a rapid protein–protein interaction of ERα-c-Src-PI3K, resulting in the activation of PI3K/AKT pathway leading to mammalian target of rapamycin (mTOR) phosphorylation. The mTOR then stimulates translation by phosphorylating p70 S6 kinase and 4EB-P1, modulating HIF-1α protein synthesis. Oestradiol-stimulated HIF-1α activity was inhibited by either siRNA or pharmacological inhibitors to ERα, c-Src, PI3K and mTOR, providing a mechanism for the modulation of HIF-1α protein synthesis.Conclusion:These results show oestradiol-induced expression of HIF-1α, downstream of the ERα/c-Src/PI3K/AKT/mTOR pathway in human breast cancer cells.

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A new class of zinc oxide quantum dots (ZnO QDs) was investigated as nanoprobes for targeting cancer cells in vitro. ZnO nanoparticles were synthesized using conventional sol-gel method and encapsulated using trimethoxy aminopropyl silane. Transferrin, the ligand targeting the cancer cells, was conjugated to the ZnO QDs. In vitro imaging studies using MDA-MB-231 showed the biocompatible ZnO nanoprobe selectively binding to the cell surface receptor and internalizing through receptor-mediated endocytosis. Time-lapsed photobleaching studies indicate the ZnO QDs to be resistant to photobleaching, making them suitable for long term imaging purpose. Investigation of the ZnO nanoprobe as a platform for sensitive bioassays indicates that it can be used as an alternative fluoroprobe for cancer cell targeting and sensing applications.

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Ferulic acid and 4-vinylguaiacol could serve as a potential structure for the development of new small molecule therapeutics against EGFR.