Yamamura M, Amano Y, Sakagami H, Yamanaka Y, Nishimoto Y, Yoshida H, Yamaguchi M, Ohata H, Momose K, Takeda M
Department of Biochemistry, School of Medicine, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Anticancer Res. 1998 Jul-Aug;18(4A):2499-502.
Nicotine dose-dependently induced cytotoxicity in human glioma (KG-1-C) and glioblastoma (GBS-1, T98G) cell lines, but could not induce internucleosomal DNA cleavage, in contrast to apoptosing human myelogenous leukemic cell lines. Human glioma/glioblastoma cell lines thus might have a chromatin structure resistant to endonuclease digestion. Nicotine induced a rapid increase in the intracellular calcium concentration. Confocal experiments with Fluo-3 fluorescence revealed that nicotine elevated the free Ca2+ concentration in both nuclear and cytoplasmic regions of the cells, and the elevation of Ca2+ in the nuclear region was more pronounced than that of the cytoplasmic region. The present study suggests that nuclear accumulation of Ca2+ is an important initial step for cell death induction by nicotine.
尼古丁剂量依赖性地诱导人胶质瘤(KG-1-C)和胶质母细胞瘤(GBS-1、T98G)细胞系产生细胞毒性,但与凋亡的人骨髓性白血病细胞系不同,它不能诱导核小体间DNA裂解。因此,人胶质瘤/胶质母细胞瘤细胞系可能具有抗核酸内切酶消化的染色质结构。尼古丁可迅速提高细胞内钙浓度。用Fluo-3荧光进行的共聚焦实验表明,尼古丁提高了细胞核和细胞质区域的游离Ca2+浓度,且细胞核区域Ca2+的升高比细胞质区域更明显。本研究表明,Ca2+的核内积累是尼古丁诱导细胞死亡的重要初始步骤。