A novel phenoxazine derivative suppresses proliferation of human endometrial adenocarcinoma cell lines, inducing G2M accumulation and apoptosis.
A novel phenoxazine derivative suppresses proliferation of human endometrial adenocarcinoma cell lines, inducing G2M accumulation and apoptosis.
复制标题
一种新型吩恶嗪衍生物可抑制人子宫内膜腺癌细胞系的增殖，诱导 G2M 积累和细胞凋亡。
DOI：
10.3892/or.10.5.1171
复制
发表时间：
2003
期刊：
影响因子：
4.2
通讯作者：
M. Takayama
中科院分区：
文献类型：
--
作者：
Toshihide Nakada;K. Isaka;H. Nishi;Yumi Osakabe;T. Shimamoto;K. Ohyashiki;A. Tomoda;M. Takayama
我们研究了一种新的吩恶嗪，2-氨基-4，4 α-二氢-4 α，7-二甲基-3H-吩恶嗪-3-酮（Phx），它是由2-氨基-5-甲基苯酚与牛血红蛋白反应产生的，对人子宫内膜腺癌细胞系EN和KLE细胞增殖的影响，以及对这些细胞凋亡和G2 M阻滞的诱导。Phx以剂量和时间依赖性方式抑制这些细胞系的增殖，即，50 μ M Phx作用2d后，EN和KLE细胞的增殖抑制率分别为43%和40%，100 μ M Phx作用2d后，EN和KLE细胞的增殖抑制率分别为75%和接近100%。当这些子宫内膜腺癌细胞与含有100 μ M Phx的培养基孵育24小时时，通过流式细胞术证实EN和KLE细胞在S和G2 M期以及凋亡细胞的积累。由Phx引起的这些细胞的凋亡不太可能与p53、Bax和Bcl-2相关，因为这些蛋白质的水平没有改变，无论是否存在Phx。目前的结果表明，Phx显示抗肿瘤活性对人子宫内膜腺癌细胞系EN和KLE细胞，通过诱导细胞周期积累在S和G2 M和凋亡与p53，Bcl-2和Bax不敏感的途径。
We examined the effects of a novel phenoxazine, 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one (Phx), which was produced by the reaction of 2-amino-5-methyl-phenol with bovine hemoglobin on the proliferation of human endometrial adenocarcinoma cell lines, EN and KLE cells, and on induction of apoptosis and G2M arrest in these cells. Phx inhibited proliferation of these cell lines in a dose- and time-dependent manner, i.e., the inhibition rate of proliferation of EN and KLE cells was 43% and 40%, respectively, in the presence of 50 micro M Phx, and 75% and nearly 100%, in the presence of 100 micro M Phx, after 2 days. When these endometrial adenocarcinoma cells were incubated with a medium containing 100 micro M Phx for 24 h, accumulation of EN and KLE cells in the S and G2M phase and that of apoptotic cells were demonstrated by flow cytometry. Apoptosis of these cells caused by Phx was unlikely to be associated with p53, Bax, and Bcl-2, because the levels of these proteins were not altered regardless of the presence or absence of Phx. The present results suggest that Phx demonstrates antitumor activity against human endometrial adenocarcinoma cell lines EN and KLE cells, by inducing both cell cycle accumulation at S and G2M and apoptosis associated with p53, Bcl-2 and Bax insensitive pathways.