LL-37

LL-37 is the only human cathelicidin — a 37-amino-acid host-defence peptide cleaved from the precursor protein hCAP-18. It is part of the innate immune system and is expressed in response to infection, injury, and inflammation. It has direct antimicrobial activity and, uniquely, direct cancer cell-killing activity via membrane disruption — but its role in cancer is complex and context-dependent.

Properties

Amino Acid Sequence

LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES

Origin: Naturally produced by neutrophils, macrophages, mast cells, NK cells, and epithelial cells

Directly disrupts cancer cell membranes via electrostatic interaction with negatively charged phospholipids (overexpressed in cancer cells vs. normal cells), causing necrotic and apoptotic death without requiring receptors. Also activates monocytes, NK cells, and dendritic cells. Promotes wound healing via chemokine release. In some contexts LL-37 can be pro-tumorigenic (ovarian, lung) while anti-tumorigenic in others (gastric, colon, melanoma) — making context critical.

Direct cytotoxicity demonstrated against melanoma, colorectal cancer, gastric cancer, and leukaemia cell lines. In melanoma specifically, LL-37 disrupts cell membranes selectively. In gastric cancer, LL-37 expression is reduced (suggesting tumour suppression role). However, in ovarian and lung cancer, LL-37 is overexpressed and may promote tumour growth — so its use is cancer-type specific. Research is exploring LL-37-drug conjugates as targeted delivery systems.

Links open on PubMed (National Library of Medicine). Research is ongoing — results may not reflect clinical use.

• Dual role: anti-tumour in some cancers, potentially pro-tumorigenic in others (ovarian, lung) — cancer-type specificity is critical
• Very short serum half-life due to protease degradation — delivery is a major challenge
• No approved therapeutic form; early-stage research compound
• Strong anti-inflammatory effects may mask infection signs
• May cause local injection site inflammation