Document Detail


Anti-tumor effects of the peptide TMTP1-GG-D(KLAKLAK)(2) on highly metastatic cancers.
MedLine Citation:
PMID:  22984407     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Xiangyi Ma; Ling Xi; Danfeng Luo; Ronghua Liu; Shu Li; Yan Liu; Liangsheng Fan; Shuangmei Ye; Wanhua Yang; Shuhong Yang; Li Meng; Jianfeng Zhou; Shixuan Wang; Ding Ma
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-09-11
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-09-17     Completed Date:  2013-03-12     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e42685     Citation Subset:  IM    
Affiliation:
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Antigens, CD95 / metabolism
Antineoplastic Agents / pharmacology,  therapeutic use*
Apoptosis / drug effects
Cell Line, Tumor
Cell Movement / drug effects
Cell Proliferation / drug effects
Disease Models, Animal
Disease Progression
Drug Delivery Systems
Humans
Male
Mice
Mice, Nude
Mitochondria / drug effects,  metabolism
Molecular Sequence Data
Neoplasm Invasiveness
Neoplasm Metastasis
Peptides / chemistry,  pharmacology,  therapeutic use*
Prostatic Neoplasms / drug therapy*,  pathology*
Signal Transduction / drug effects
Stomach Neoplasms / drug therapy*,  pathology*
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/Antigens, CD95; 0/Antineoplastic Agents; 0/FAS protein, human; 0/Peptides; 0/TMTP1-glycylglycyl-(lysyl-leucyl-alanyl-lysyl-leucyl-alanyl-lysyl)2
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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