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KMID : 0043320120350050791
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Archives of Pharmacal Research
2012 Volume.35 No. 5 p.791 ~ p.799
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Anticancer activity of undecapeptide analogues derived from antimicrobial peptide, Brevinin-1EMa
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Kang Su-Jin
Ji Hye-Young
Lee Bong-Jin
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Abstract
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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-NH2) (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-NH2), 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.
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KEYWORD
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Anticancer peptides, Antimicrobial peptides, Synergistic effects, Combination index, Dose reduction index
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