The Antimicrobial Peptide Melectin Shows Both Antimicrobial and Antitumor Activity via Membrane Interference and DNA Binding

Abstract

Increasingly complex diseases require novel drugs for their treatment. Antimicrobial peptides (AMPs) are promising candidate treatments due to their broad existence and special characteristics. However, the current understanding of AMPs is not sufficient to allow them to be produced commercially for clinical use. Materials and Methods: Melectin, from the venom of the cleptoparasitic bee Melecta albifrons, does not exhibit sequence homology with other wasp venom peptides. To investigate this more deeply, we explored the antibacterial and antitumor activities of Melectin and related mechanisms. Results: Our results demonstrate that Melectin possesses antimicrobial properties against standard sensitive/clinical drug-resistant bacteria strains as well as antitumor activity. It has an α-helix form and exhibits moderate cytotoxicity. Its action mechanisms are involved with membrane interfering and DNA binding. The membrane interfering effect was distinct between different phospholipid compositions. Conclusion: We found that Melectin may serve as a new potential template in the battle against multidrug resistance, and our study indicated that there are promising prospects for medically applicable drugs based on AMPs.

A Review on Genotoxic and Genoprotective Effects of Biologically Active Compounds of Animal Origin

“…Melectin, an antimicrobial peptide from the venom of the cleptoparasitic bee Melecta albifrons , does not exhibit sequence homology with other wasp venom peptides. Melectin manifests antitumour activity, penetrates membranes and binds DNA [ 38 ]. The venom of a parasitoid wasp, Pteromalus puparum, contains a peptide with endonuclease activity (PpENVP), which inhibits gene expression in transfected cells relying on two activation sites [ 71 ].…”

Pharmacological effects and mechanisms of bee venom and its main components: Recent progress and perspective

“…Besides, melectin reduced the release of TNF-α, IL-1β, IL-6, and IL-8 from S. aureus -stimulated human fibroblasts. These findings suggested that melectin could be considered as a new template against multidrug resistance ( Ko et al, 2020 ; Liang et al, 2021 ).…”

“…In addition to inhibiting cell viability, MEL had high permeability to the plasma membrane of cells in human acute T cell leukemia Jurkat cells, which enhanced the permeability of MEL through the plasma membrane and further caused cell death ( Gasanoff et al, 2021 ). The anti-infectivity peptide melectin from Melecta albifrons , by virtue of its α-helical structure, inhibited cell proliferation by interfering with the cell membrane of leukemic cells K562, decreasing the viability of various cells such as K562, K562/ADM and HL-60 while enhancing LDH output ( Liang et al, 2021 ).…”

“…Besides, the Selective Index of NIH3T3 (healthy mouse fibroblast cells) was higher than 3 compared to HepG2 and MDA-MB-231 cells, implying that BV was more selective for both types of cancer cells and that NIH3T3 showed altered cell morphology only when BV was 100 μg/ml ( Uzuner et al, 2021 ). Moreover, Melectin at around 15 μM only slightly inhibited NIH3T3; Concentration below 50 μM caused only 20% erythrocyte lysis, with no significant hemolytic effect ( Liang et al, 2021 ). Comparable results existed for MEL-AF treatment, where MEL-AF remained non-significantly cytotoxic at doses in the range of ≤10 μg/ml after 24 h of MEL-AF treatment ( Sangboonruang et al, 2020 ).…”

Antimicrobial Peptides with Anti-Candida Activity

“…Melectin shows low hemolytic activity [ 211 ], and, in mammalian cancer cells, this peptide mainly targets the cell membrane, and, after penetrating the cell, it is able to compromise the whole cell’s integrity [ 199 ]. Asides from that, melectin is also able to bind to plasmid DNA [ 213 ].…”