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

Biomedicines

Teerapong Siriboonpiputtana¹  Jirawan Panachan²  Thitinee Vanichapol²  Suradej Hongeng²  Pongpak Pongphitcha²  Sarayut Supapannachart³  Pracha Nuntnarumit³  Chantragan Srisomsap⁴  Jisnuson Svasti⁴  Somchai Chutipongtanate⁵  Wararat Chiangjong⁵  Nutkridta Pongsakul⁵  Tassanee Lerksuthirat⁶ 

[1] Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand;Department of Pediatrics, Division of Hematology and Oncology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand;Division of Neonatology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand;Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand;Pediatric Translational Research Unit, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand;Research Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand;

关键词: anticancer peptide;    drug discovery;    human milk;    leukemia;    machine learning;    mass spectrometry;   

DOI  :  10.3390/biomedicines9080981

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown