Kaneko H, Hibasami H, Satoh N, Wakabayashi H, Ikeda H, Tsuge N, Yonemaru K, Muraki A, Kawarada Y, Nakashima K
Department of Biochemistry and First Surgery, Faculty of Medicine, Mie University, Tsu-city, Mie 514-8507, Japan.
Int J Mol Med. 1998 Jun;1(6):931-6. doi: 10.3892/ijmm.1.6.931.
Polyamines are considered to be important intracellular molecules for the proliferation of the cancer cells. In this study, effects of methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP), a potent inhibitor of the polyamine biosynthetic pathway, on the growth and cell cycle of T-47D human breast cancer cells were investigated. MGBCP dose-dependently inhibited the growth of T-47D cells, in which the contents of spermine, spermidine and putrescine decreased concomitantly. The gene expression of cyclin D1 was also repressed by the MGBCP treatment. The MGBCP-treated cells clearly exhibited morphological changes indicating the blebbing and chromatin condensation which are characteristic of apoptosis. Flow cytometric analysis showed hypo-diploid subpopulations due to apoptotic cells, and characteristic oligonucleosomal-sized DNA fragments were clearly observed for MGBCP-treated cells as the concentration of the drug was increased. These findings suggest that the inhibition of polyamine synthesis results in the repressions of cyclin D1 expression and cell cycle progression, eventually inducing apoptosis in these human breast cancer cells.
多胺被认为是癌细胞增殖过程中重要的细胞内分子。在本研究中，我们研究了多胺生物合成途径的强效抑制剂甲基乙二醛双（环戊基脒腙）（MGBCP）对T-47D人乳腺癌细胞生长和细胞周期的影响。MGBCP剂量依赖性地抑制T-47D细胞的生长，同时精胺、亚精胺和腐胺的含量也随之降低。MGBCP处理还抑制了细胞周期蛋白D1的基因表达。经MGBCP处理的细胞明显表现出形态变化，表明出现了凋亡特征性的泡状突起和染色质凝聚。流式细胞术分析显示，由于凋亡细胞导致出现亚二倍体亚群，并且随着药物浓度的增加，在经MGBCP处理的细胞中明显观察到特征性的寡核小体大小的DNA片段。这些发现表明，多胺合成的抑制导致细胞周期蛋白D1表达和细胞周期进程受到抑制，最终诱导这些人乳腺癌细胞凋亡。
