Abstract
Aim: Anticancer immunochemotherapy represents an attractive paradigm to improve therapeutic responses and reduce side effects. Results & methodology: Here, we show that a naturally occurring host defense peptide, HN-1 inhibited multiple malignant cells proliferation and tumor growth in a xenografted human breast tumor model. Acting through MAPK/NF-κB pathways, HN-1 induced a caspase-independent mitochondrial apoptosis, as indicated by a p53-dependent increase of Bax/Bcl-2 ratio and the nuclear translocation of apoptosis inducing factor. Besides, HN-1 augmented CD4+/CD8+ T cells in 4T1 mammary carcinoma model, by enhancing the serum levels of cancer immunity-associated effectors. Meanwhile, HN-1 decreased the angiogenesis and infiltration of the tumor-associated macrophages. Conclusion: HN-1 induces caspase-independent cancer cells apoptosis and boosts cancer-resolving immunity without inducing potentially harmful pro-inflammatory responses.
Supplementary data
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Financial & competing interests disclosure
This work was supported by the Chinese National Natural Science Foundation (31872223 and 31772455); Natural Science Foundation of Jiangsu Province (BK20160336 and BK20171214); Natural Science Foundation of College in Jiangsu Province (16KJB350004); Suzhou Science and Technology Development Project (SNG2017045); Qinglan Project of Jiangsu Education Department, the Priority Academic Program Development of the Jiangsu Higher Education Institutes (PAPD). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.