Soto-Domínguez Adolfo, Ballesteros-Elizondo Raquel G, Santoyo-Pérez Martha E, Rodríguez-Rocha Humberto, García-Garza Rubén, Nava-Hernández Martha P, Villa-Cedillo Sheila A, Montes-de-Oca-Luna Roberto, Saucedo-Cárdenas Odila
Universidad Autónoma de Nuevo León, Facultad de Medicina, Departamento de Histología, Madero y Dr. Aguirre Pequeño, Mitras Centro, Monterrey, Nuevo León, 64460, Mexico.
Universidad Autónoma de San Luis Potosí, Facultad de Medicina, Departamento de Ciencias Morfológicas, Av. Venustiano Carranza 2405, C.P. 78210, San Luis Potosí, S.L.P., Mexico.
Toxicon. 2018 Nov;154:79-89. doi: 10.1016/j.toxicon.2018.09.010. Epub 2018 Sep 28.
Karwinskia parvifolia possesses the highest concentration levels of the anthracenone T-514 (PA1). Studies have demonstrated the induction of apoptosis by PA1 in cancer cell lines. The aim was to investigate the effects of PA1 on the apoptosis of the mouse liver in vivo and its underlying pathway. Sixty CD-1 mice were divided into three groups: untreated, vehicle, and treated with PA1. The animals were euthanized at 4, 8, 12, and 24 h post-treatment. To confirm the toxic effect of PA1 we determined the activity of catalase. Liver sections were prepared for morphological examination and for immunohistochemical evaluation of anti and pro-apoptotic markers. DNA fragmentation was detected by TUNEL assay and electrophoresis. Pre-apoptotic mitochondrial alterations and cytochrome c oxidase activity were analyzed by transmission electron microscopy. PA1 induced pre-apoptotic mitochondrial alterations, a high activity of the cytochrome oxidase, and apoptosis in hepatocytes. PA1 caused p53 over-expression and down regulation of PCNA. PA1 also increased the expression levels of the pro-apoptotic markers Bax and Bak, whereas the anti-apoptotic molecule Bcl-2 was decreased. PA1 induces apoptosis by activating the intrinsic mitochondrial apoptotic pathway. These results will be useful for studies regarding the use of PA1 as an antineoplastic agent.
小叶卡氏桐含有最高浓度的蒽酮T - 514（PA1）。研究已证明PA1可在癌细胞系中诱导细胞凋亡。目的是研究PA1对小鼠肝脏体内细胞凋亡的影响及其潜在途径。将60只CD - 1小鼠分为三组：未处理组、溶剂对照组和PA1处理组。在处理后4、8、12和24小时对动物实施安乐死。为证实PA1的毒性作用，我们测定了过氧化氢酶的活性。制备肝脏切片用于形态学检查以及抗凋亡和促凋亡标志物的免疫组织化学评估。通过TUNEL检测和电泳检测DNA片段化。通过透射电子显微镜分析凋亡前的线粒体改变和细胞色素c氧化酶活性。PA1诱导凋亡前的线粒体改变、细胞色素氧化酶的高活性以及肝细胞凋亡。PA1导致p53过表达和PCNA下调。PA1还增加了促凋亡标志物Bax和Bak的表达水平，而抗凋亡分子Bcl - 2减少。PA1通过激活内源性线粒体凋亡途径诱导细胞凋亡。这些结果将有助于关于PA1作为抗肿瘤药物用途的研究。
