Ponente
Descripción
Mammalian neutral aminopeptidase also known as Aminopeptidase N (APN, EC
3.4.11.2) is the most extensively studied member of the M1-family of zinc-dependent
aminopeptidases. This enzyme catalyzes the cleavage of neutral and basic amino
acids from the N-terminus of protein or peptide substrates leading to their
activation/inactivation. APN is widely expressed on cell surfaces of tissues, such as
intestinal epithelia, renal cortex, and the nervous system. APN plays important roles in
many physiological processes such as pain sensation, sperm motility, cell-cell
adhesion, and blood pressure regulation. Change in APN expression in different
tissues, particularly upregulation of the activity of this enzyme are related with different
human malignancies, including several types of cancers. This makes APN a potential
target for the treatment of cancer and the development of new APN inhibitors is of
current interest. The objective of this research was to preliminarily characterize the
possible inhibition of APN by bestatin, bacitracin and the YTE series compounds, and
the possible cytotoxicity of bestatin and bacitracin on the APN+ tumor line of human
melanoma MeWo (HTB-65). As a result of this investigation, it was concluded that the
tested inhibitors inhibited porcine APN in vitro with different pre-incubation times and
with a dose dependent behavior; bestatin and bacitracin did not show marked cytotoxic
effects on the normal murine line of NIH/3T3 (CRL-1658) fetal fibroblasts but MeWo
(HTB-65) cell line was susceptible to being inhibited by bestatin and bacitracin without
appreciable effects on any specific stage of the cell cycle; although, both induced DNA
fragmentation.
References
[1] Schreiber, C. L., & Smith, B. D. (2018). Molecular imaging of aminopeptidase N in cancer and angiogenesis. Contrast media & molecular imaging, 2018.
[2] Tieku, T., Hooper, M. (1992) Inhibition of aminopeptidases N, A and W: a re-evaluation of the actions of bestatin and inhibitors of angiotensin converting enzyme. Biochemical pharmacol 44, 17251730.
[3] Amin, S. A., N. Adhikari, Jha, T. (2018) Design of aminopeptidase N inhibitors as anticancer agents. J. Med. Chem. 61(15): 6468-6490
[4] Mucha, A., Drag, M., Dalton, J.P., Kafarski, P. (2010) Metallo-aminopeptidase inhibitors. Bioch. 92: 1509-1529.
