title: Anti-tumor effects of the peptide TMTP1-GG-D(KLAKLAK)(2) on highly metastatic cancers.
abstract: The treatment of cancer such as oligonucleotides or peptides requires efficient delivery systems. A novel peptide, TMTP1, previously derived and identified in our laboratory showed remarkable ability to target highly metastatic tumors both in vitro and in vivo, even at the early stage of occult metastasis foci. TMTP1 moderately inhibited tumor cell viability, although not enough to deem it an efficient killer of tumor cells. In this study, we sought to enhance the anti-tumor activity of TMTP1. To do this, we fused it to an antimicrobial peptide, (D)(KLAKLAK)(2), and termed the resulting peptide TMTP1-DKK. We found that TMTP1-DKK could trigger rapid apoptosis in human prostate and gastric cancer cells through both the mitochondrial-induced apoptosis pathway and the death receptor pathway. Furthermore, direct injection of TMTP1-DKK into mice with prostate and gastric xenograft cancers resulted in reduction of tumor volumes and a significant delay in tumor progression and metastasis in vivo. These results suggest that TMTP1-DKK may serve as a powerful therapeutic agent for metastatic tumors.
authors.affiliation: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Xiangyi
authors.initials: X
authors.lastname: Ma
authors.forename: Ling
authors.initials: L
authors.lastname: Xi
authors.forename: Danfeng
authors.initials: D
authors.lastname: Luo
authors.forename: Ronghua
authors.initials: R
authors.lastname: Liu
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Liangsheng
authors.initials: L
authors.lastname: Fan
authors.forename: Shuangmei
authors.initials: S
authors.lastname: Ye
authors.forename: Wanhua
authors.initials: W
authors.lastname: Yang
authors.forename: Shuhong
authors.initials: S
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Meng
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhou
authors.forename: Shixuan
authors.initials: S
authors.lastname: Wang
authors.forename: Ding
authors.initials: D
authors.lastname: Ma
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D016503:Drug Delivery Systems; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays; D019014:fas Receptor / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C491901:FAS protein, human; D010455:Peptides; C578777:TMTP1-glycylglycyl-(lysyl-leucyl-alanyl-lysyl-leucyl-alanyl-lysyl)2; D019014:fas Receptor