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

Kengo Kuroda,Hiroshi Isogai,Emiko Isogai,Kazuhiko Okumura

doi:10.3389/fonc.2015.00144

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.

Highlights

Antimicrobial peptides (AMPs) are host defense molecules of the innate immune system of all life forms [1, 2]
We showed that FF/CAP18 treatment inhibits the proliferation of these cancer cell lines, and results in apoptosis and cell death
The interaction between LL-37, which has a cationic charge, and the negatively charged membrane of cancer cells is extremely important with respect to the development of new therapeutic strategies, and we review the current understanding of these interactions

Summary

Introduction

Antimicrobial peptides (AMPs) are host defense molecules of the innate immune system of all life forms [1, 2]. Human cationic antibacterial protein of 18 kDa (hCAP18, called LL-37 or FALL39) is the only cathelicidin in humans, and is primarily found in the secondary granules of neutrophils [6, 7]; LL-37 is released as an active domain from macrophages/monocytes and various epithelial cells [8, 9]. Antimicrobial peptides were initially identified as functional antimicrobial molecules They have been characterized as multifunctional peptides that serve a variety of biological roles, Anticancer effect of human LL-37 such as immune regulation, wound healing, angiogenesis, and anticancer functions. Their anticancer activity depends on cancer types.

Cell types

Cell Types

Interaction between AMPs and the Cancer Membrane

Conclusion and Future Challenges