Membrane active antitumor activity of NK-18, a mammalian NK-lysin-derived cationic antimicrobial peptide.
As the increasing emergence of multi-drug resistant tumor cells, there is an urgent need for developing new chemotherapeutic agents. NK-lysin was a novel effector of cytotoxic T cells and natural killer (NK) cells and had broad antimicrobial activity. In this study, we developed a core region of NK-lysin termed NK-18, and studied its antitumor activity and possible action mode. Our results showed that NK-18 (with 18 amino acids) possesses potent antitumor activity against bladder and prostate cancer cells by disrupting the integrity of cell membrane, but has negligible hemolysis activity against mouse erythrocytes. In addition, CD spectra was employed to study its conformation in membrane mimicking environment. NK-18 takes a standard α-helical conformation in membrane mimicking environment, which could be accounted for its more potent antitumor activity compared with its low α-helical content homologous derivatives. These findings together with its shorter amino acid sequence and lower synthesis cost suggest that NK-18 could present an alternative therapeutic strategy to cancer chemotherapy and play a promising role in fighting the multi-drug resistant tumors.
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 222 South Tianshui Road, Lanzhou 730000, PR China.
Jie-xi
JX
Yan
Kai-rong
KR
Wang
Ru
R
Chen
Jing-jing
JJ
Song
Bang-zhi
BZ
Zhang
Wen
W
Dang
Wei
W
Zhang
Rui
R
Wang
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning
D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; C571367:NK-18 peptide