Journal
MOLECULAR AND CELLULAR BIOCHEMISTRY
Volume 385, Issue 1-2, Pages 79-86Publisher
SPRINGER
DOI: 10.1007/s11010-013-1816-2
Keywords
hMnSOD-R9; Expression; DNA damage protection; Trans-membrane; Apoptosis
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Funding
- National Natural Science Foundation of China [30700704]
- Science and Technology Innovation Project from Department of Education of Guangdong Province [2012KJCX0017]
- Key Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences [KLRB201105]
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Human manganese superoxide dismutase (hMnSOD) is a new type of cancer suppressor. Nonamer of arginine (R9) is an efficient protein transduction domain (PTD). The aim of the study was to improve the transduction efficiency of hMnSOD and investigate its activity in vitro. In this study, we designed, constructed, expressed, and purified a novel fusion protein containing the hMnSOD domain and R9 PTD (hMnSOD-R9). The DNA damaged by Fenton's reagent was found to be significantly reduced when treated with hMnSOD-R9. hMnSOD-R9 fusion protein was successfully delivered into HeLa cells. The MTT assay showed that proliferation of various cancer cell lines were inhibited by hMnSOD-R9 in a dose-dependent manner. In addition, the cell cycle of HeLa cells was arrested at the sub-G0 phase by hMnSOD-R9. hMnSOD-R9 induced apoptosis of HeLa cells in a dose-dependent manner. With hMnSOD-R9 treatment, Bax, JNK, TBK1 gene expression was increased and STAT3 gene expression was gradually down-regulated in HeLa cells. We also found that apoptosis was induced by hMnSOD-R9 in HeLa cells via up-regulation of cleaved caspase-3 and down-regulation phospho-STAT3 pathway. These results indicated that hMnSOD-R9 may provide benefits to cervical cancer treatment.
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