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A recombinant trans-membrane protein hMnSOD–R9 inhibits the proliferation of cervical cancer cells in vitro

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Abstract

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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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (30700704), Science and Technology Innovation Project from Department of Education of Guangdong Province (2012KJCX0017) and the Key Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences (KLRB201105).

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Authors and Affiliations

  1. Institute of Genomic Medicine, College of Pharmacy, **an University, Guangzhou, 510632, China

    Zide Zhang, Qiuhong Wu, Enze Yang, Guang Zhang, Hanxiao Sun & Feng Wang

  2. Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, **an University, Guangzhou, 510632, China

    Zide Zhang, Qiuhong Wu, Enze Yang, Guang Zhang, Hanxiao Sun & Feng Wang

  3. Chinese Academy of Sciences Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510633, China

    Luyuan Huang

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  1. Zide Zhang
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Correspondence to Feng Wang.

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Zhang, Z., Huang, L., Wu, Q. et al. A recombinant trans-membrane protein hMnSOD–R9 inhibits the proliferation of cervical cancer cells in vitro. Mol Cell Biochem 385, 79–86 (2014). https://doi.org/10.1007/s11010-013-1816-2

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