The Human Cathelicidin Antimicrobial Peptide LL-37 and Mimics are Potential Anticancer Drugs

Abstract

Antimicrobial peptides (AMPs) play a critical role in innate host defense against microbial pathogens in many organisms. The human cathelicidin, LL-37, has a net positive charge and is amphiphilic, and can eliminate pathogenic microbes directly via electrostatic attraction toward negatively charged bacterial membranes. A number of studies have shown that LL-37 participates in various host immune systems, such as inflammatory responses and tissue repair, in addition to its antibacterial properties. Moreover, recent evidence suggests that it is also involved in the regulation of cancer. Indeed, previous studies have suggested that human LL-37 is involved in carcinogenesis via multiple reporters, such as FPR2 (FPRL1), epidermal growth factor receptor, and ERBb2, although LL-37 and its fragments and analogs also show anticancer effects in various cancer cell lines. This discrepancy can be attributed to peptide-based factors, host membrane-based factors, and signal regulation. Here, we describe the association between AMPs and cancer with a focus on anticancer peptide functions and selectivity in an effort to understand potential therapeutic implications.

Identification of human cathelicidin peptide LL-37 as a ligand for macrophage integrin α_Mβ₂ (Mac-1, CD11b/CD18) that promotes phagocytosis by opsonizing bacteria

“…The immunomodulatory effects of LL-37 have been ascribed to its binding to and/or modulating activity of several unrelated cell surface receptors such as FPRL 1, EGFR, P2X 7 , and others. 12,[16][17][18][19]42 In this study, we demonstrated that LL-37 is a ligand for the major integrin receptor Mac-1 (CD11b/CD18) on the surface of myeloid cells and found that coating of bacteria with LL-37 augments Mac-1-mediated …”

The structure and functions of lactoferrin and its role in human reproduction (a review)

“…Таким образом, они пришли к выводу, что ЛФ является маркером степе-ни зрелости нейтрофилов, а вторичные гранулы ней-трофилов являются секреторными, как первичные. Благодаря этим гранулам осуществляется элимина-ция ЛФ в экстрацеллюлярное пространство и повы-шение его уровня в плазме крови [11].…”

Roles and Mechanisms of Human Cathelicidin LL-37 in Cancer

“…Cathelicidins are antimicrobial peptides produced by mammals in response to various pathogenic microbes [1][2][3][4][5]. Human cathelicidin antimicrobial peptide (CAMP, hCAP-18) is the only member of the cathelicidin protein family in humans [1][2][3][4][5].…”

“…Human cathelicidin antimicrobial peptide (CAMP, hCAP-18) is the only member of the cathelicidin protein family in humans [1][2][3][4][5]. hCAP-18 (18kDa) is processed by proteolytic cleavage to bioactive cathelicidin LL-37 (37 amino acid residues with diLeucine at the N-terminus) by exposure to specific serine proteases like proteinase 3, kallikrein 5 and kallikrein 7 [1].…”

“…Human cathelicidin antimicrobial peptide (CAMP, hCAP-18) is the only member of the cathelicidin protein family in humans [1][2][3][4][5]. hCAP-18 (18kDa) is processed by proteolytic cleavage to bioactive cathelicidin LL-37 (37 amino acid residues with diLeucine at the N-terminus) by exposure to specific serine proteases like proteinase 3, kallikrein 5 and kallikrein 7 [1]. hCAP-18 is widely expressed in various epithelial cells Ovarian cancer LL-37 expression levels significantly increase in ovarian cancer tissues compared to the normal ovary tissues suggesting it might be a potential biomarker of ovarian cancer [2,35].…”