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3-氨基苯甲酰胺在A431癌细胞中的抗增殖活性与对细胞骨架的靶向作用有关。

Antiproliferative activity of 3-aminobenzamide in A431 carcinoma cells is associated with a target effect on cytoskeleton.

作者信息

Tiozzo R, Monti D, Straface E, Capri M, Croce M A, Rainaldi G, Franceschi C, Malorni W

机构信息

Department of Biomedical Science, University of Modena, Italy.

出版信息

Biochem Biophys Res Commun. 1996 Aug 23;225(3):826-32. doi: 10.1006/bbrc.1996.1258.

Abstract

3-Aminobenzamide (3-ABA) is an inhibitor of poly(ADP-ribose)polymerase (PARP), an enzyme involved in several cellular processes, and exerts its effects by acting at the cytoskeleton level. Here we show that 3-ABA has an antiproliferative effect on the human carcinoma cell line A431, as measured by different assays. 3-ABA was capable of inhibiting cell growth as well as colony formation, this inhibitory effect is reversible. Morphological analyses showed a series of cellular alterations, such as a remarkable increase of dendritic-like protrusions, quite unusual in epithelial cells, and suggestive of a differentiative triggering. Immunocytochemical studies suggested that a major target of 3-ABA was indeed the cytoskeleton. These data, together with those of the literature, indicate that 3-ABA, depending on cell histotype and drug concentration, is a versatile drug capable of exerting antiproliferative and cytostatic effects as well as cytotoxic and antiapoptotic effects, processes sharing an important involvement of cytoskeleton. These unique characteristics of 3-ABA may be of interest for cancer research.

摘要

3-氨基苯甲酰胺(3-ABA)是聚(ADP-核糖)聚合酶(PARP)的抑制剂,PARP是一种参与多种细胞过程的酶,它通过作用于细胞骨架水平发挥其作用。在此我们表明,通过不同检测方法测定,3-ABA对人癌细胞系A431具有抗增殖作用。3-ABA能够抑制细胞生长以及集落形成,这种抑制作用是可逆的。形态学分析显示了一系列细胞改变,例如树突状突起显著增加,这在上皮细胞中相当罕见,提示有分化触发。免疫细胞化学研究表明3-ABA的主要靶点确实是细胞骨架。这些数据以及文献数据表明,取决于细胞组织类型和药物浓度,3-ABA是一种多功能药物,能够发挥抗增殖和细胞抑制作用以及细胞毒性和抗凋亡作用,这些过程都与细胞骨架的重要参与有关。3-ABA的这些独特特性可能对癌症研究具有重要意义。

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