Cancer has always been one of the most common malignant diseases in the world. Therefore, there is an urgent need to find potent agents with selective antitumor activity against
cancer cells. It has been reported that
antimicrobial peptides (AMPs) can selectively target
tumor cells. In this study, we focused on the anti-
tumor activity and mechanism of Brevinin-1RL1, a cationic α-helical
AMP isolated from frog Rana limnocharis skin secretions. We found that Brevinin-1RL1 preferentially inhibits
tumor cells rather than non-
tumor cells with slight hemolytic activity. Cell viability assay demonstrated the intermolecular
disulfide bridge contributes to the inhibitory activity of the
peptide as the antitumor activity was abolished when the
disulfide bridge reduced. Further mechanism studies revealed that both
necrosis and apoptosis are involved in Brevinin-1RL1 mediated
tumor cells death. Moreover, Brevinin-1RL1 induced extrinsic and mitochondria intrinsic apoptosis is
caspases dependent, as the pan-
caspase inhibitor
z-VAD-FMK rescued Brevinin-1RL1 induced
tumor cell proliferative inhibition. Immunohistology staining showed Brevinin-1RL1 mainly aggregated on the surface of the
tumor cells. These results together suggested that Brevinin-1RL1 preferentially converges on the
cancer cells to trigger
necrosis and caspase-dependent apoptosis and Brevinin-1RL1 could be considered as a pharmacological candidate for further development as anti-
cancer agent.