The antitumor activity and preliminary modeling on the potential mechanism of action of human peroxiredoxin-5
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Juanjuan Liu1, Xiaozhou Feng1, Yuanyuan Jin1, Zhengyang Sun1, Haoyi Meng1, Zhifei Zhang2, Laixing Hu1, Zhaoyong Yang1
1Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
2College of Pharmaceutical Sciences, North China University of Science and Technology, Tangshan, People’s Republic of China
Zhifei Zhang, email: [email protected]
Laixing Hu, email: [email protected]
Zhaoyong Yang, email: [email protected]
Keywords: anti-cancer bioactive peptide, human peroxiredoxin-5, antitumor activity, immunoregulation, PD-L1
Received: January 11, 2017 Accepted: February 20, 2017 Published: March 10, 2017
Goat peroxiredoxin-5 (gPRDX5) was verified as a good anti-cancer bioactive peptide (ACBP) against different tumor cell lines. Considering the immunogenicity between species for further therapeutic application, it is necessary to similarly investigate the antitumor activity of human peroxiredoxin-5 (hPRDX5) with 89% similarity in sequence to gPRDX5. In order to evaluate its antitumor activity, the potential anti-neoplastic effect of hPRDX5 on a mouse model was observed directly. The results of its in vivo antitumor activity suggested that hPRDX5 could resist immunosuppression by promoting lymphocyte proliferation and up-regulating the levels of serum cytokines. Meanwhile, PD-L1 was speculated as one of the targets of hPRDX5 to inhibit tumor by enhancing the immune activity according to a preliminary molecular docking study on the interactions between hPRDX5 and PD-L1. The modeling provides a basis for structural modification on hPRDX5/PD-L1 for further biological and biochemical study on the pathway blocking mechanism of hPRDX5. In this work, the results demonstrate that hPRDX5 displays efficient antitumor and immunoregulatory properties in the colon cancer C26/BALB/c and melanoma B16/C57Bl/6 mice tumor models, and suggest the potential of developing peptides from hPRDX5 as low molecular weight drug candidates for corresponding cancer immunotherapy.
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