Induction of G2/M phase arrest and apoptosis by potent antitumor APCA in human cervix carcinoma cells
Induction of G2/M phase arrest and apoptosis by potent antitumor APCA in human cervix carcinoma cells
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DOI：
10.1097/cad.0b013e328349597d
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发表时间：
2011-10
影响因子：
2.3
通讯作者：
Ke Xu;Xin Liang;F. Wang;Lijuan Xie;Yufang Xu;Jianwen Liu;X. Qian
中科院分区：
文献类型：
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作者：
Ke Xu;Xin Liang;F. Wang;Lijuan Xie;Yufang Xu;Jianwen Liu;X. Qian
3-(二甲基氨基-乙基氨基)-8-氧代-8H-苊酚[1, 2-b]吡咯-9-羧酸 (APCA) 作为一种有效的抗肿瘤化合物，对一系列已建立的癌细胞表现出抗癌活性。同时，APCA对正常人体细胞的细胞毒作用远小于对癌细胞的细胞毒作用。本研究调查了 APCA 诱导 HeLa 细胞生长抑制的分子机制。结果表明，APCA 诱导的细胞周期停滞在 G2/M 期，与 cyclinB1 和细胞周期蛋白依赖性激酶 1 以 p53 无关的方式表达下调相关，并且还导致细胞凋亡增加，这一点通过特征性形态学变化和凋亡亚 G1 群体增加得到证实。此外，在APCA处理的HeLa细胞中观察到核因子B的易位抑制、Bax的上调以及Bcl-2、caspase-3和caspase-9的激活以及聚（ADP-核糖）聚合酶裂解的下调，这表明线粒体途径参与了细胞凋亡信号途径。总之，APCA 通过 HeLa 细胞的细胞周期阻滞和凋亡诱导表现出抗肿瘤作用，这表明 APCA 可能作为有效的先导化合物具有治疗宫颈癌的潜力。
3-(dimethylamino-ethylamino)-8-oxo-8H-acenaphthol[1, 2-b]pyrrole-9-carboxylic acid (APCA), as a potent antitumor compound, showed anticancer activity on a series of established cancer cells. Meanwhile, the cytotoxic effects of APCA were much smaller on normal human cells than that on cancer cells. This study investigated the molecular mechanisms underlying APCA-induced growth inhibition in HeLa cells. The results showed that the APCA-induced cell cycle arrest at G2/M phase correlated with cyclinB1 and cyclin-dependent kinase 1 expression downregulation in a p53-independent manner, and also caused an increase in apoptosis, which was confirmed by characteristic morphological changes and increased apoptotic sub-G1 population. Furthermore, translocation inhibition of nuclear factor-B, upregulation of Bax, and downregulation of Bcl-2, caspase-3 and caspase-9 activation, and poly-(ADP-ribose) polymerase cleavage were observed in HeLa cells treated with APCA, which indicated that the mitochondrial pathway was involved in the apoptosis signal pathway. In summary, APCA displayed an antitumor effect through cell cycle arrest and apoptotic induction in HeLa cells, which suggested that APCA might have therapeutic potential against cervix carcinoma as an effective lead compound.