Abstract
Mere15 is a novel polypeptide from Meretrix meretrix Linnaeus with cytotoxicity in solid cancer cells. In this study, we investigated its activity on human K562 chronic myelogenous leukemia cells. Mere15 inhibited the growth of K562 cells with IC50 values of 38.2 μg/mL. Mere15 also caused concentration dependent induction of apoptosis, with overproduction of reactive oxygen species and loss of mitochondrial membrane potential. Moreover, Mere15 arrested cell cycle progression at G0/G1 phase of K562 cells in a concentration dependent manner. In addition, Mere15 caused the disassembly of the microtubule cytoskeleton in K562 cells and inhibited the polymerization of tubulin in a cell free system via interaction with tubulin. We concluded that Mere15 was cytotoxic to K562 leukemia cells and the cytotoxicity was related to the apoptosis induction, cell cycle arrest and microtubule disassembly. These results implied that Merer15 was a broad spectrum anticancer polypeptide, not only cytotoxic to various solid cancer cells but also to the chronic myelogenous leukemia cells. Mere15 may have therapeutic potential for the treatment of leukemia.
Highlights
Marine organisms are a rich resource for discovering novel anticancer drugs [1,2]
We evaluated the cytotoxicity of Mere15 on human K562 chronic myelogenous leukemia cells
The cytotoxicity of Mere15 on K562 cell lines was evaluated by MTT assay
Summary
Marine organisms are a rich resource for discovering novel anticancer drugs [1,2]. A lot of peptides from marine source display potent anticancer activity [3]. Didemnin, a cyclic depsipeptides isolated from the Caribbean tunicate Trididemnun solidum, is the first marine peptide that entered in clinical trials in US for the treatment of cancer [4]. Administration for the treatment of Hodgkin’s lymphoma and systemic anaplastic large cell lymphoma [6] These researches suggest that it is a promising strategy to search anticancer peptides/proteins from the marine organisms. Recent studies have shown that certain peptides and/or proteins derived from M. meretrix are contributed to their anticancer activity. Mere exhibits significant cytotoxicity to several solid cancer cell lines via apoptotic pathway [10]. Our previous research was only confined to the solid cancer cell lines; whether Mere could be cytotoxic to hematological malignant tumors remains unknown.
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