title: NAHA, a novel hydroxamic acid-derivative, inhibits growth and angiogenesis of breast cancer in vitro and in vivo.
abstract: BACKGROUND
  We have recently synthesized novel N-alkylated amino acid-derived hydroxamate, 2-[Benzyl-(2-nitro-benzenesulfonyl)-amino]-N-hydroxy-3-methyl-N-propyl-butyramide (NAHA). Here, we evaluate the anticancer activity of NAHA against highly invasive human breast cancer cells MDA-MB-231 in vitro and in vivo.
  
  
  RESULTS
  Cell growth was evaluated by MTT and soft agar assays. Protein expression was determined by DNA microarray and Western blot analysis. Metastatic potential was evaluated by cell adhesion, migration, invasion, capillary morphogenesis, and ELISA assays. The anticancer activity in vivo was evaluated in mouse xenograft model. NAHA inhibited proliferation and colony formation of MDA-MB-231 cells together with the down-regulation of expression of Cdk2 and CDC20 proteins. NAHA inhibited cell adhesion, migration, and invasion through the suppression of secretion of uPA. NAHA suppressed secretion of VEGF from MDA-MB-231 cells and inhibited capillary morphogenesis of human aortic endothelial cells (HAECs). Finally, NAHA at 50 mg/kg was not toxic and decreased tumor volume and tumor weight in vivo. This suppression of tumor growth was associated with the inhibition of mitotic figures and induction of apoptosis, and the reduction of CD31 and VEGF positive cells in tumors.
  
  
  CONCLUSIONS
  NAHA could be a novel promising compound for the development of new drugs for the therapy of invasive breast cancers.
authors.affiliation: Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, Indiana, United States of America.
authors.forename: Jiahua
authors.initials: J
authors.lastname: Jiang
authors.forename: Anita
authors.initials: A
authors.lastname: Thyagarajan-Sahu
authors.forename: Viktor
authors.initials: V
authors.lastname: Krchňák
authors.forename: Andrej
authors.initials: A
authors.lastname: Jedinak
authors.forename: George E
authors.initials: GE
authors.lastname: Sandusky
authors.forename: Daniel
authors.initials: D
authors.lastname: Sliva
mesh_terms: D000577:Amides / Q000737:chemistry*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry*; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D008956:Models, Chemical; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D014633:Valine / Q000031:analogs & derivatives* / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C575961:2-(benzyl-(2-nitrobenzenesulfonyl)amino)-N-hydroxy-3-methyl-N-propylbutyramide; D000577:Amides; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; D042461:Vascular Endothelial Growth Factor A; C006866:butyramide; D014633:Valine