The antitumor activity and preliminary modeling on the potential mechanism of action of human peroxiredoxin-5

Abstract

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.