Anticancer activity of undecapeptide analogues derived from antimicrobial peptide, Brevinin-1EMa

Abstract

In spite of great advances in cancer therapy, cancer remains the major cause of death throughout the world. The increasing resistance of cancer cells towards current anticancer drugs requires development of anticancer agents with a new mode of action. Some antimicrobial peptides have become therapeutic candidates as new anticancer agents. As part of an effort to develop new antimicrobial and/or anticancer agents from natural peptides with low molecular weights, we have investigated the shortest bioactive analogues, which were derived from a 24-residue antimicrobial peptide, Brevinin-1EMa. Recently, we found four bioactive undecapeptides derived from a cationic, amphipathic α-helical, 11-residue peptide (named herein GA-W2: FLGWLFKWASK-NH(2)) (Won et al., 2011). In order to identify the potential of these peptides as anticancer agents, we investigated the anticancer activity of four undecapeptides against seven tumor cell lines such as A498 (kidney), A549 (lung), HCT116 (colon), MKN45 (stomach), PC-3 (prostate), SK-MEL-2 (skin) and SK-OV-3 (ovary). GA-K4 (FLKWLFKWAKK-NH(2)), which had the most potent antimicrobial activity of the four undecapeptides, also exhibited the most potent anticancer activity and synergistic effect in combination with doxorubicin. Therefore, GA-K4 peptide may be a potentially useful candidate as an anticancer peptide agent.

Biological Properties, Current Applications and Potential Therapeautic Applications of Brevinin Peptide Superfamily

“…Additionally, anti-cancer properties of Brevinin-1EMa derivatives were investigated against seven tumor cell lines, such as A498 (kidney), A549 (lung), HCT116 (colon), MKN45 (stomach), PC-3 (prostate), SK-MEL-2 (skin), and SK-OV-3 (ovary). (Kang et al 2012). There was a report concerning the anti-cancer function of modified Brevinin, like dicarba-Brevinin-1BYa.…”

Medicinal plants: used in Anti-cancer treatment

“…In this investigated the anticancer activity of four undecapeptides against seven tumor cell lines such as A498 (kidney), A549 (lung), HCT116 (colon), MKN45 (stomach), PC-3 (prostate), SK-MEL-2 (skin) and SK-OV-3 (ovary). Result showed that the GA-K4 (FLKWLFKWAKK-NH2), which had the most potent antimicrobial activity of the four undecapeptides, also exhibited the most potent anticancer activity snf synergistic effect in combination with doxorubicin [20].…”

Evaluating the Bioactivity of a Novel Broad-Spectrum Antimicrobial Peptide Brevinin-1GHa from the Frog Skin Secretion of Hylarana guentheri and Its Analogues

“…Then some researches revealed some common structural features of Brevinin-1 family, Proline is often the 14th residue in the sequence [ 10 ], and most of them have a cyclic heptapeptide (Cys 18 -(Xaa)4-Lys-Cys 24 ) called Rana-box at the C-terminal, which forms a disulfide bridge [ 11 ]. Brevinin-1 peptides usually demonstrate a broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria and strains of pathogenic fungi [ 9 ], and some analogues can inhibit the growth of cancer cell lines [ 12 ]. Peptides in the Brevinin-1 family are linear, amphipathic and cationic.…”