An Anionic Cathelicidin Exerts Antimelanoma Effects in Mice by Promoting Pyroptosis

While
cationic antimicrobial peptides (AMPs) are extensively studied
for antitumor effects, anionic AMPs remain underexplored. Notably,
no amphibian-derived anionic cathelicidins with antitumor activity
have been reported. This study identifies Boma-CATH, a novel anionic
cathelicidin (net charge–3) from Bombina maxima skin, which suppresses melanoma growth in mice and triggers pyroptosis-like
morphological changes in A375 cells via the NLRP3/Caspase-1/GSDMD
pathway. Further investigation revealed that ROS played a crucial
role in promoting pyroptosis, as NAC (ROS scavenger) and Ac-YVAD-cmk
(Caspase-1 inhibitor) reversed cell death and reduced LDH/IL-1β
release in vitro and in vivo. GSDMD knockdown further validated its
role. Additionally, Boma-CATH inhibited A375 cell proliferation, migration,
and invasion, demonstrating dual antitumor mechanisms: pyroptosis
induction and metastasis suppression. Importantly, Boma-CATH caused
no adverse effects in mice, highlighting its therapeutic safety. These
findings position Boma-CATH as a promising melanoma treatment and
expand the mechanistic understanding of anionic AMPs in oncology.