title: Enhanced antitumor effects of the BRBP1 compound peptide BRBP1-TAT-KLA on human brain metastatic breast cancer.
abstract: Novel molecularly targeted agents that block the development and metastasis of human brain metastatic breast cancer hold great promise for their translational value. In this study, we constructed a novel targeting composite peptide BRBP1-TAT-KLA comprising of three elements: a brain metastatic breast carcinoma cell (231-BR)-binding peptide BRBP1, a cell penetrating peptide TAT, and a proapoptotic peptide KLA. This composite peptide efficiently internalized in 231-BR cells and consequently induced mitochondrial damage and cellular apoptosis. Exposure of 231-BR cells to BRBP1-TAT-KLA significantly decreased cell viability and increased apoptosis compared with the cells treated with the control peptides. In vivo relevance of these findings was further corroborated in the 231-BR tumor-bearing mice that demonstrated significantly delayed tumor development and metastasis following administration of BRBP1-TAT-KLA compared with those treated with TAT-KLA alone. Interestingly, BRBP1-TAT-KLA inhibited the formation of both large and micro-metastases, while TAT-KLA alone failed to significantly reduce micro-metastases in the breast cancer brain metastasis mice. BRBP1-TAT-KLA selectively homed to the tumors in vivo where it induced cellular apoptosis without significant toxicity on non-tumor tissues. Our findings therefore demonstrated the enhanced antitumor effects of the BRBP1 compound peptide BRBP1-TAT-KLA, providing insights toward development of a potential therapeutic strategy for brain metastatic breast cancer.
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease, Ministry of Education; Medical School, Southeast University, Nanjing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Fu
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease, Ministry of Education; Medical School, Southeast University, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Long
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease, Ministry of Education; Medical School, Southeast University, Nanjing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease, Ministry of Education; Medical School, Southeast University, Nanjing, China.
authors.forename: Aifeng
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease, Ministry of Education; Medical School, Southeast University, Nanjing, China.
authors.forename: Fengqin
authors.initials: F
authors.lastname: Miao
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease, Ministry of Education; Medical School, Southeast University, Nanjing, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease, Ministry of Education; Medical School, Southeast University, Nanjing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Pan
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease, Ministry of Education; Medical School, Southeast University, Nanjing, China.
authors.forename: Guangming
authors.initials: G
authors.lastname: Gan
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging; Department of Radiology, Zhongda Hospital; Medical School, Southeast University, Nanjing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Nie
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease, Ministry of Education; Medical School, Southeast University, Nanjing, China.
authors.forename: Youji
authors.initials: Y
authors.lastname: He
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease, Ministry of Education; Medical School, Southeast University, Nanjing, China.
authors.forename: Jianqiong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging; Department of Radiology, Zhongda Hospital; Medical School, Southeast University, Nanjing, China.
authors.forename: Gaojun
authors.initials: G
authors.lastname: Teng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D015696:Gene Products, tat / Q000008:administration & dosage / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D009842:Oligopeptides / Q000235:genetics*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000235:genetics; D010455:Peptides / Q000008:administration & dosage / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: C000604864:BRBP1 peptide; D015696:Gene Products, tat; D036341:Intercellular Signaling Peptides and Proteins; C535058:KLA peptide; D009842:Oligopeptides; D010446:Peptide Fragments; D010455:Peptides