Toninello Antonio, Pietrangeli Paola, De Marchi Umberto, Salvi Mauro, Mondovì Bruno
Department of Biological Chemistry University of Padua and C.N.R. Institute of Neuroscience, Unit for the Study of Biomembranes, Viale G. Colombo 3, 35121 Padua, Italy.
Biochim Biophys Acta. 2006 Jan;1765(1):1-13. doi: 10.1016/j.bbcan.2005.09.001. Epub 2005 Sep 29.
Amine oxidases, the major enzymes of biogenic amines metabolism, are considered to be biological regulators, especially for cell growth and differentiation. A primary involvement of amine oxidases in cancer growth inhibition and progression, especially by means of aldehydes, H(2)O(2) and other reactive oxygen species, the amine oxidase-mediated products of biogenic amines oxidation, has been demonstrated. Amine oxidases are involved in cancer growth inhibition because of the higher content in tumour cells of biogenic amines in comparison to normal cells. The cytotoxic effect can be explained by a damage to cell membranes and/or nuclei or, indirectly, through modulation of membrane permeability transition and therefore apoptosis. The oxidation products of biogenic amines appears to be also carcinogenic, while acrolein, produced from the oxidation of spermine and spermidine, should be a key compound both carcinogenic and cytotoxic. The cancer inhibition/promotion effect of amine oxidases could be explained by taking into consideration the full pattern of the enzyme content of the cell. The balance of amine oxidases and antioxidant enzymes appear to be a crucial point for cancer inhibition or progression. A long lasting imbalance of these enzymes appears to be carcinogenic, while, for a short time, amine oxidases are cytotoxic for cancer cells.
胺氧化酶是生物胺代谢的主要酶类,被认为是生物调节剂,特别是对细胞生长和分化而言。胺氧化酶在癌症生长抑制和进展中起主要作用,尤其是通过醛、H₂O₂和其他活性氧物质,这些是生物胺氧化的胺氧化酶介导产物,这一点已得到证实。与正常细胞相比,由于肿瘤细胞中生物胺含量较高,胺氧化酶参与癌症生长抑制。细胞毒性作用可以通过对细胞膜和/或细胞核的损伤来解释,或者间接通过调节膜通透性转变从而导致细胞凋亡来解释。生物胺的氧化产物似乎也具有致癌性,而由精胺和亚精胺氧化产生的丙烯醛应该是一种兼具致癌性和细胞毒性的关键化合物。考虑到细胞中酶含量的完整模式,可以解释胺氧化酶的癌症抑制/促进作用。胺氧化酶和抗氧化酶的平衡似乎是癌症抑制或进展的关键点。这些酶的长期失衡似乎具有致癌性,而在短时间内,胺氧化酶对癌细胞具有细胞毒性。