title: Antitumor effects, cell selectivity and structure-activity relationship of a novel antimicrobial peptide polybia-MPI.
abstract: A novel antimicrobial peptide, polybia-MPI, was purified from the venom of the social wasp Polybia paulista. It has potent antimicrobial activity against both Gram-positive and Gram-negative bacteria, but causing no hemolysis to rat erythrocytes. To date, there is no report about its antitumor effects on any tumor cell lines. In this study we synthesized polybia-MPI and studied its antitumor efficacy and cell selectivity. Our results revealed that polybia-MPI exerts cytotoxic and antiproliferative efficacy by pore formation. It can selectively inhibit the proliferation of prostate and bladder cancer cells, but has lower cytotoxicity to normal murine fibroblasts. In addition, to investigate the structure-activity relationship of polybia-MPI, three analogs in which Leu7, Ala8 or Asp9 replaced by L-Pro were designed and synthesized. L-Pro substitution of Leu7 or Asp9 significantly reduces the content of alpha-helix conformation, and L-Pro substitution of Ala8 can disrupt the alpha-helix conformation thoroughly. The L-Pro substitution induces a significant reduction of antitumor activity, indicating that the alpha-helix conformation of polybia-MPI is important for its antitumor activity. In summary, polybia-MPI may offer a novel therapeutic strategy in the treatment of prostate cancer and bladder cancer, considering its relatively lower cytotoxicity to normal cells.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, Lanzhou University, 222 South Tianshui Road, Lanzhou 730000, PR China.
authors.forename: Kai-rong
authors.initials: KR
authors.lastname: Wang
authors.forename: Bang-zhi
authors.initials: BZ
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Jie-xi
authors.initials: JX
authors.lastname: Yan
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D049109:Cell Proliferation / Q000187:drug effects; D016895:Culture Media, Serum-Free; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005347:Fibroblasts / Q000187:drug effects / Q000648:ultrastructure; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000502:physiology; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000502:physiology; D006461:Hemolysis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008297:Male; D051379:Mice; D041681:NIH 3T3 Cells; D011392:Proline / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000648:ultrastructure; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D051381:Rats; D013329:Structure-Activity Relationship; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000648:ultrastructure; D014862:Wasp Venoms / Q000737:chemistry / Q000633:toxicity; D014863:Wasps / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D016895:Culture Media, Serum-Free; D014862:Wasp Venoms; D011392:Proline; D007770:L-Lactate Dehydrogenase