NAHA, a novel hydroxamic acid-derivative, inhibits growth and angiogenesis of breast cancer in vitro and in vivo

Jiahua Jiang, Anita Thyagarajan-Sahu, Viktor Krchňák, Andrej Jedinak, George Sandusky, Daniel Sliva

Research output: Contribution to journalArticle

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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. Methodology/Principal Findings: 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. Conclusion: NAHA could be a novel promising compound for the development of new drugs for the therapy of invasive breast cancers.

Original languageEnglish
Article numbere34283
JournalPLoS One
Volume7
Issue number3
DOIs
StatePublished - Mar 29 2012

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hydroxamic acids
Hydroxamic Acids
angiogenesis
breast neoplasms
Tumors
chemical derivatives
Breast Neoplasms
Derivatives
neoplasms
Cell adhesion
Growth
cell adhesion
Vascular Endothelial Growth Factor A
morphogenesis
Assays
Tumor Burden
Morphogenesis
Cell Adhesion
Cells
secretion

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

NAHA, a novel hydroxamic acid-derivative, inhibits growth and angiogenesis of breast cancer in vitro and in vivo. / Jiang, Jiahua; Thyagarajan-Sahu, Anita; Krchňák, Viktor; Jedinak, Andrej; Sandusky, George; Sliva, Daniel.

In: PLoS One, Vol. 7, No. 3, e34283, 29.03.2012.

Research output: Contribution to journalArticle

Jiang, Jiahua ; Thyagarajan-Sahu, Anita ; Krchňák, Viktor ; Jedinak, Andrej ; Sandusky, George ; Sliva, Daniel. / NAHA, a novel hydroxamic acid-derivative, inhibits growth and angiogenesis of breast cancer in vitro and in vivo. In: PLoS One. 2012 ; Vol. 7, No. 3.
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