An integrative approach leads to the discovery of a novel anti-leukemic peptide from human milk

Abstract

Chemotherapy in childhood leukemia is associated with late morbidity in leukemic survivors, while certain patient subsets relatively resistant to standard chemotherapy. Identifying new agents with the sensitivity and selectivity toward leukemic cells with less systemic toxicity is a warrant. Peptide-based therapeutics is gaining attention during the last few years. Here, we used an integrative workflow combining mass spectrometric peptide library construction, in silico anticancer peptide screening, and in vitro leukemic cell studies to discover a novel anti-leukemic peptide owning 3+ charges and alpha-helical structure, namely HMP-S7, from human breast milk. HMP-S7 showed cytotoxic activity against four distinct leukemic cell lines in a dose-dependent manner but had no affected on solid malignancies or representative normal cells. HMP-S7 induced leukemic cell death by penetrating the plasma membrane into the cytoplasm, causing lactate dehydrogenase leakage, thereby defining membranolytic action. In conclusion, HMP-S7 is the selective anti-leukemic peptide promising for further validation in preclinical and clinical studies.