Arminin 1a-C, a novel antimicrobial peptide from ancient metazoan <em>Hydra</em>, shows potent antileukemia activity against drug-sensitive and drug-resistant leukemia cells

Abstract

PurposeDue to the emergence of multidrug resistance (MDR), traditional antileukemia drugs no longer meet the treatment needs. Therefore, new antileukemia drugs with different action mechanisms are urgently needed to cope with this situation.Materials and methodsArminin 1a-C is an antimicrobial peptide (AMP) developed from the ancient metazoan marine Hydra. In this study, we first explored its antileukemia activity.ResultsOur results showed that Arminin 1a-C formed an α-helical structure and efficaciously suppressed the viability of leukemia cell lines whether or not they were multidrug resistant or sensitive, and there were no obvious differences between these cell lines. Arminin 1a-C exhibited distinct selectivity between noncancerous and cancerous cell lines. Arminin 1a-C interfered with K562/adriamycin (ADM) cell (a kind of multidrug-resistant leukemia cell line) proliferation in a very rapid manner and formed pores in its cell membrane, making it difficult to develop resistance against Arminin 1a-C.ConclusionOur data show that Arminin 1a-C possesses great potential as a therapeutic candidate for the treatment of multidrug-resistant leukemia.

Equinins as Novel Broad-Spectrum Antimicrobial Peptides Isolated from the Cnidarian Actinia equina (Linnaeus, 1758)

“…Hydramacin-1 (purified from Hydra), has been proven to have microbiocidal activity inducible by microbial substances, e.g., dose-dependent lipopolysaccharide, and is capable of inhibiting the growth of some Gram-positive (Bacillus megaterium) and Gram-negative (E. coli, Klebsiella oxytoca, and Klebsiella pneumoniae) bacteria [10]. Similarly to what has been observed in A. equina, Arminin identified in H. magnipapillata did not show toxicity to human erythrocytes (a crucial indicator of biocompatibility) and is characterized by a negative charge with a highly conserved N-terminal region and a poorly preserved positively charged C-terminal region [32]; Arminin 1a-C, an antimicrobial peptide with an α-helical structure from ancient metazoan Hydra, efficaciously suppressed the viability of leukaemia cell lines, whether or not they were MDR or sensitive, and independently of the cell lines considered, also exhibiting a distinct discernment between noncancerous and cancerous cell lines [33]. The relevance of the structural characteristics of the bioactive molecules in defining their properties suggests that the different MICs needed to prompt an antibacterial response between the purified A. equina AMPs and the synthesized peptide may be attributable to the conformational needs of the molecule itself.…”

Antimicrobial Peptide Brevinin-1RL1 from Frog Skin Secretion Induces Apoptosis and Necrosis of Tumor Cells

“…The LDH release assay was performed by the CytoTox 96 non-radioactive cytotoxicity assay kit (Promega; Charbonnie’res-les-Bains, France) according to the manufacturer’s protocol as previously described [ 54 ]. Briefly, cells seeded in 96-well plates (5 × 10 3 cells/well/100 μL) were incubated with various concentrations of Brevinin-1RL1 or equivalent DMSO for 24 h. Then, cells were lysed for 45 min served as the spontaneous and maximum LDH activity controls for 45 min before running the assay.…”

Coelenterate Toxins, Its Pharmaceutical and Therapeutic Effects

“…Seaanemone also contain cytolysins which have Kunitz-type protease inhibitors activity. These toxins efficiently kill Giardia cells and show anti-parasite specificity with anti-Giardia antibodies [49] (fig. 3).…”