Renovation as innovation: Repurposing human antibacterial peptide LL-37 for cancer therapy

Abstract

In many organisms, antimicrobial peptides (AMPs) display wide activities in innate host defense against microbial pathogens. Mammalian AMPs include the cathelicidin and defensin families. LL37 is the only one member of the cathelicidin family of host defense peptides expressed in humans. Since its discovery, it has become clear that they have pleiotropic effects. In addition to its antibacterial properties, many studies have shown that LL37 is also involved in a wide variety of biological activities, including tissue repair, inflammatory responses, hemotaxis, and chemokine induction. Moreover, recent studies suggest that LL37 exhibits the intricate and contradictory effects in promoting or inhibiting tumor growth. Indeed, an increasing amount of evidence suggests that human LL37 including its fragments and analogs shows anticancer effects on many kinds of cancer cell lines, although LL37 is also involved in cancer progression. Focusing on recent information, in this review, we explore and summarize how LL37 contributes to anticancer effect as well as discuss the strategies to enhance delivery of this peptide and selectivity for cancer cells.

Antimicrobial peptides for novel antiviral strategies in the current post‐COVID‐19 pandemic

“…Regarding the secondary structures, AMPs are classified as linear α‐helical peptides, β‐sheet peptides, peptides with extended structure, and peptides with both α‐helix and β‐sheet conformation or with more complex topologies 30 . Based on their biological activity, we can distinguish between AMPs with antibacterial, 31 antifungal, 32 antiviral, 33 antiparasitic, 34 and anticancer properties 35 . Based on their primary mechanism of action, AMPs can be divided in two major groups: non‐membrane targeting and membrane targeting AMPs, even if recent evidence showed that some AMPs not only act on the membrane but they can also activate a cascade of reactions within bacterial cells 36,37 .…”

“…30 Based on their biological activity, we can distinguish between AMPs with antibacterial, 31 antifungal, 32 antiviral, 33 antiparasitic, 34 and anticancer properties. 35 Based on their primary mechanism of action, AMPs can be divided in two major groups: non-membrane targeting and membrane targeting AMPs, even if recent evidence showed that some AMPs not only act on the membrane but they can also activate a cascade of reactions within bacterial cells. 36,37 To the first group belong the peptides that enter the cell and interact with specific targets by inhibiting intracellular processes such as protein biosynthesis, 38 nucleic acid biosynthesis, 39 protease activity and cell division.…”

Shaping the Future of Antimicrobial Therapy: Harnessing the Power of Antimicrobial Peptides in Biomedical Applications

“…Biomedical Application Peptide Surgical site infection (SSI) LL-37 [15], hBD2&3 [16], Protegrins [17], Histatins [18], Ranalexin [19], Pexiganan [20], Magainin [21], HNP1 [22] Contact lens-associated microbial keratitis (CLMK) α-MSH [23], Melimine [24], Pexiganan [25], Bacitracin [26], Dermcidin [27] Dental applications LL-37 [28], Dermaceptin [29], Nisin, Histatins [30], hBD1 [31], human beta-defensin-3 [32], human beta-defensin-5, Cateslytin [33], Myxinidin [34], HHC-36 [34] Bone-graft applications KLD [35], E14LKK [36] Tissue generation DermaceptinS4 [37], Thanatin [38], LLKKK18 [39], DPK-060 [40], SMAP-29 [41], G3KL [42], G3R, MSI-78 Anticancer agents pAntp [43], KT2 [44], RT2 [45], LL37 [46], LTX-315, [46] melittin [47]…”

Antimicrobial Peptides—Mechanisms of Action, Antimicrobial Effects and Clinical Applications

“…Although the exact mechanism of wound repair is still elusive, there is a supposed effect of LL-37 in modulating the inflammatory response and driving angiogenesis together with re-epithelialization [ 125 , 141 ]. Such a wide array of modulatory cell activities also led to the repurposing of LL-37 for cancer treatment [ 142 ]. Moreover, its role in oral homeostasis is also known, and it is not related merely to microbiota stabilization [ 143 ].…”