RRC ID 43731
著者 Horibe T, Kawamoto M, Kohno M, Kawakami K.
タイトル Cytotoxic activity to acute myeloid leukemia cells by Antp-TPR hybrid peptide targeting Hsp90.
ジャーナル J Biosci Bioeng
Abstract We previously reported that Antp-TPR hybrid peptide inhibited the interaction of Hsp90 with TPR2A and had selective cytotoxic activity discriminating between normal and cancer cells to induce cancer cell death. In this study, we investigated the cytotoxic activity of Antp-TPR peptide toward acute myeloid leukemia (AML) cells. It was demonstrated that Antp-TPR peptide induced AML cell death in cell lines such as U937, K562, THP-1, and HL-60 via activation of caspases 3 and 7, and disruption of mitochondrial membrane potential. Conversely, Antp-TPR peptide did not reduce the viability of normal cells including peripheral blood mononuclear cells (PBMCs), although both geldanamycin and 17-AAG, small-molecule inhibitors of Hsp90, mediated cytotoxicity to these normal cells at low concentrations. In addition, mutation analysis of TPR peptide demonstrated that the highly conserved amino acids Lys and Arg were critical to the cytotoxic activity. These results indicated that Antp-TPR hybrid peptide would provide potent and selective therapeutic options in the treatment of AML.
巻・号 114(1)
ページ 96-103
公開日 2012-7-1
DOI 10.1016/j.jbiosc.2012.02.016
PII S1389-1723(12)00077-1
PMID 22425524
MeSH Amino Acid Sequence Amino Acids / metabolism Animals Antineoplastic Agents / pharmacology Cell Line, Tumor Cell Survival / drug effects Cells, Cultured Cytotoxins / pharmacology* HEK293 Cells HL-60 Cells HSP90 Heat-Shock Proteins / antagonists & inhibitors* HSP90 Heat-Shock Proteins / chemistry Homeodomain Proteins / chemistry Homeodomain Proteins / metabolism Homeodomain Proteins / pharmacology* Humans Inhibitor of Apoptosis Proteins / genetics Inhibitor of Apoptosis Proteins / metabolism Inhibitory Concentration 50 K562 Cells Leukemia, Myeloid, Acute / pathology Leukocytes, Mononuclear / cytology Leukocytes, Mononuclear / drug effects* MCF-7 Cells Mice Mice, Inbred C57BL Molecular Sequence Data Protein Structure, Tertiary Sequence Alignment Survivin Tumor Suppressor Proteins / chemistry Tumor Suppressor Proteins / metabolism U937 Cells
IF 2.366
引用数 8
WOS 分野 FOOD SCIENCE & TECHNOLOGY BIOTECHNOLOGY & APPLIED MICROBIOLOGY
リソース情報
ヒト・動物細胞 293(RCB1637)