| Summary: | 碩士 === 輔仁大學 === 營養科學系碩士班 === 103 === The nucleolus is the organelle of the nucleus which the place for the ribosome biogenesis, including of ribosomal RNA (rRNA) transcription, pre-rRNA processing and ribosomal assembly. Nucleolar morphologic-functional changes and ribosome biogenesis have been shown to coordinate with regulation of cell proliferation. Elevated cellular iron indicates demand for growth of cancer cells, therefore decreasing iron level by iron chelator results in inhibiting of cancer cell growth. Whether the iron chelator inhibits cell proliferation associate with nucleolar structural-functional changes is still unrevealed. In this study, a total of 3430 proteins from MCF-7 human breast cancer cells were identified by using of stable isotope dimethyl label coupled with LC/MS/MS. Two hundred fifty eight proteins were up-regulated, and 164 proteins were down-regulated in iron chelator deferoxamine (DFO)-treated cells for 48hr. Most of these up-regulated proteins are involved in rRNA processing, ribosome synthesis, and apoptosis/cell death. In contrast, most of the down-regulated proteins are involved in energy metabolism, protein metabolic process, cell cycle, and cell proliferation. DFO treatment for 48h caused the cell cycle arrest at G0/G1 phase by using flow cytometry. In addition, DFO treatment also caused nucleolar morphologic changes, and reduced its content by 27% by using AgNOR staining. The rRNA processing relative ribonucleoprotein Nop58 and folding-protein Ero1L-α were increased by 11.4 and 0.6 fold in DFO treatment, respectively. In contrast, the ribosome export adaptor NMD3 was reduced by 60 % in DFO-treated cells. In summary, iron chelator inhibits the cell growth may associate with nucleolar morphologic-functional changes.
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