A lab-made short version of the natural peptide LL-37, called 17BIPHE2, was shown to kill lung cancer cells in dishes and slow tumor growth in animals by triggering cell death pathways and messing with a signaling route called ERK.

In 2018, there were 18.1 million new cancer cases and 9.6 million cancer-related deaths worldwide, among which the incidence rate of lung cancer (11.6%) and fatality rate (18.4%) both ranked first. The antimicrobial peptide LL-37 is an important component of the natural immune system and possesses several biological properties, including antibacterial, antiviral and anticancer effects. The antimicrobial peptide 17BIPHE2, the shortest synthetic peptide derivative of LL-37, exhibits biological activities similar to those of LL-37. The objective of the present study was to investigate the mechanism of action of exogenous 17BIPHE2 against lung cancer cells. The human lung adenocarcinoma cell line A549 was treated with 17BIPHE2. Changes in cell proliferation, migration, invasion, mitochondrial membrane potential (ΔΨm), and the levels of reactive oxygen species (ROS), Ca²⁺ and apoptosis-related proteins, including BAX, BCL-2 and ERK, were detected using flow cytometry, transmission electron microscopy and western blotting. The results showed that 17BIPHE2 significantly increased the apoptosis rate of A549 cells and elevated BAX expression, ERK phosphorylation, and ROS and Ca²⁺ levels, but decreased the expression of BCL-2, ERK and Ki67. In addition, the peptide reduced ΔΨm and the cell migration ability of A549 cells and inhibited tumor growth. ERK inhibition significantly attenuated the anticancer effect of 17BIPHE2. The present observations suggested that 17BIPHE2 can effectively inhibit cancer cells by regulating the ERK signaling pathway.