HMP-S7 Is a Novel Anti-Leukemic Peptide Discovered from Human Milk.

Wararat Chiangjong,Pracha Nuntnarumit,Thitinee Vanichapol,Nutkridta Pongsakul,Jirawan Panachan,Teerapong Siriboonpiputtana,Jisnuson Svasti,Somchai Chutipongtanate,Tassanee Lerksuthirat,Sarayut Supapannachart,Pongpak Pongphitcha,Suradej Hongeng,Chantragan Srisomsap

doi:10.3390/biomedicines9080981

Wararat Chiangjong, Pracha Nuntnarumit + Show 11 more

Open Access

https://doi.org/10.3390/biomedicines9080981

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Abstract

Chemotherapy in childhood leukemia is associated with late morbidity in leukemic survivors, while certain patient subsets are relatively resistant to standard chemotherapy. It is therefore important to identify new agents with sensitivity and selectivity towards leukemic cells, while having less systemic toxicity. Peptide-based therapeutics has gained a great deal of 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 having 3+ charges and an 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 effect on solid malignancies or representative normal cells. HMP-S7 induced leukemic cell death by penetrating the plasma membrane to enter the cytoplasm and cause the leakage of lactate dehydrogenase, thus acting in a membranolytic manner. Importantly, HMP-S7 exhibited anti-leukemic effects against patient-derived leukemic cells ex vivo. In conclusion, HMP-S7 is a selective anti-leukemic peptide with promise, which requires further validation in preclinical and clinical studies.

Highlights

Cancer is a significant cause of death in children and adolescents during the last few years in Asia, Central and South America, Northwest Africa, and the Middle East [1].Hematologic malignancies, acute lymphocytic leukemia (ALL), are predominant, accounting for 30% of childhood cancers [2]
The results showed that human milk milk peptides peptides (HMPs)-S7, the most highly charged cationic peptide with an α-helical structure, had higher inhibitory activity than the other human-milk-derived peptides towards four leukemic cell lines, including
The results demonstrated the antileukemic activity of HMP-S7 was dose-dependent, with the IC50 ranging from 89.2 to 186.3 μM depending on the leukemic cell tested

Summary

Introduction

Hematologic malignancies, acute lymphocytic leukemia (ALL), are predominant, accounting for 30% of childhood cancers [2]. Biomedicines 2021, 9, 981 regimens during the past decades has resulted in more than a remission rate of 90% in childhood ALL [3]. Specific subsets of pediatric ALL are relatively resistant to standard chemotherapy and have high risk of relapse [6]. These challenges stress the need to further improve current treatment, while identifying new agents with sensitivity and selectivity toward leukemic cells with little to no toxicity to normal cells

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