We have demonstrated that the peptide L-2 designed from an alanine scanning of the Limulus-derived LALF32-51 region is a potential candidate for the anticancer therapy and its cell-penetrating capacity is an associated useful property. By the modification in the primary structure of L-2, a second-generation peptide (CIGB-552) was developed. However, the molecular mechanism underlying its cytotoxic activity remains partially unknown. In this study, it was shown that CIGB-552 increases the levels of COMMD1, a protein involved in copper homeostasis, sodium transport, and the NF-κB signaling pathway. We found that CIGB-552 induces ubiquitination of RelA and inhibits the antiapoptotic activity regulated by NF-κB, whereas the knockdown of COMMD1 blocks this effect. We also found that CIGB-552 decreases the antioxidant capacity and induces the peroxidation of proteins and lipids in the tumor cells. Altogether, this study provides new insights into the mechanism of action of the peptide CIGB-552, which could be relevant in the design of future anticancer therapies.
Lugo JM, Tafalla C, Oliva A, et al. Evidence for antimicrobial and anticancer activity of pituitary adenylate cyclase-activating polypeptide (PACAP) from North African catfish (Clarias gariepinus): Its potential use as novel therapeutic agent in fish and humans. Fish Shellfish Immunol. 2019;86:559-570. doi:10.1016/j.fsi.2018.11.056
Fernu00e1ndez Massu00f3 JR, Oliva Argu00fcelles B, Tejeda Y, et al. The Antitumor Peptide CIGB-552 Increases COMMD1 and Inhibits Growth of Human Lung Cancer Cells. J Amino Acids. 2013;2013:251398. doi:10.1155/2013/251398