Lauricella M, Giuliano M, Emanuele S, Vento R, Tesoriere G
Institute of Biological Chemistry, University of Palermo, Policlinico, Palermo, Italy.
Tumour Biol. 1998;19(5):356-63. doi: 10.1159/000030028.
This paper deals with the apoptotic effect exerted in human retinoblastoma Y79 cells by a number of compounds. A remarkable effect was observed after treatment with DNA-damaging agents, such as camptothecin, etoposide, cisplatin and carboplatin; camptothecin was found to be the most efficacious. Treatment with these compounds induced the appearance of morphological features of apoptosis in the cells together with the distinct fragmentation of DNA, as shown by agarose gel electrophoresis. These effects were also accompanied by a remarkable increase in the level of p53. Many other compounds, which are not DNA-damaging agents, induced the morphological features of apoptosis but none of them were capable of increasing the level of p53. Among these compounds, Taxol, suramin and sodium butyrate also stimulated the oligonucleosomal fragmentation of DNA, while C2-ceramide, a cell-permeable analogue of ceramide, and vitamin D3 were not effective in the induction of DNA laddering in Y79 cells. Apoptosis was dependent on macromolecular synthesis with all the compounds tested.
本文探讨了多种化合物对人视网膜母细胞瘤Y79细胞的凋亡作用。在用DNA损伤剂(如喜树碱、依托泊苷、顺铂和卡铂)处理后观察到显著效果;发现喜树碱最为有效。用这些化合物处理诱导细胞出现凋亡的形态学特征以及DNA的明显片段化,如琼脂糖凝胶电泳所示。这些效应还伴随着p53水平的显著升高。许多其他非DNA损伤剂的化合物也诱导了凋亡的形态学特征,但它们都不能提高p53水平。在这些化合物中,紫杉醇、苏拉明和丁酸钠也刺激了DNA的寡核小体片段化,而细胞可渗透的神经酰胺类似物C2-神经酰胺和维生素D3对诱导Y79细胞中的DNA梯状条带无效。所有测试的化合物诱导的凋亡均依赖于大分子合成。