The mediating role of caspase-3 protease in the intracellular mechanism of genistein-induced apoptosis in human prostatic carcinoma cell lines, DU145 and LNCaP
The mediating role of caspase-3 protease in the intracellular mechanism of genistein-induced apoptosis in human prostatic carcinoma cell lines, DU145 and LNCaP
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DOI：
10.1016/s0248-4900(00)01109-6
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发表时间：
2000-12-01
影响因子：
2.7
通讯作者：
Hall, A
中科院分区：
文献类型：
--
作者：
Kumi-Diaka, J;Sanderson, NA;Hall, A
进行了一系列的体外研究，以调查染料木素诱导的细胞死亡，细胞死亡的性质，在两个人前列腺癌细胞系（LNCaP和Du 145），和caspase-3蛋白酶在染料木素诱导的靶细胞凋亡的可能参与。这些研究的主要发现是：i）染料木黄酮主要通过凋亡抑制LNCaP和DU 145细胞的生长和增殖，在较高浓度下通过坏死抑制LNCaP和DU 145细胞的生长和增殖：ii）染料木黄酮诱导两种靶细胞中caspase-3（CPP 32）的活化和表达; iii）半胱天冬酶-3抑制剂可显著抑制染料木素诱导的细胞凋亡和CPP 32活化，z-VAD-氟代（N-苄氧基羰基-Val-Asp-氟甲基-酮），从而证实了CPP 32在靶细胞中染料木黄酮诱导的凋亡途径中的介体作用。大多数已知的癌症化学预防药物的效力是由于在实体瘤中诱导细胞凋亡（Thompson，Science 267（1995）1456; Gurney等人，Science 288（2000）283）。不可避免地，增加半胱天冬酶-3蛋白酶的转录的试剂可以通过CPP 32介导的细胞凋亡加强细胞死亡。在这方面，染料木黄酮可能会发现在治疗人类前列腺癌，独立的激素敏感性的应用。(C)2000年，Elsevier SAS科学与医学版。
A series of in vitro studies were carried out to investigate genistein-induced cell death, and the nature of cell death, in two human prostate cancer cell lines (LNCaP and Du145), and the possible involvement of caspase-3 protease in genistein-induced apoptosis in the target cells. The major findings of these studies are: i) genistein inhibits growth and proliferation of both LNCaP and DU145 cells via apoptosis mainly, and necrosis at higher concentrations; ii) genistein induces activation and expression of caspase-3 (CPP32) in both target cells; iii) genistein-induced apoptosis and CPP32 activation could be significantly inhibited by the caspase-3 inhibitor, z-VAD-fmk (N-benzyloxycarbonyl-Val-Asp-fluoromethyl-ketone), thus confirming a mediator role of CPP32 in the genistein-induced apoptotic pathway in the target cells. The potency of most known chemopreventive drugs for cancer is due to induction of apoptosis in solid tumors (Thompson, Science 267 (1995) 1456; Gurney et al., Science 288 (2000) 283). Inevitably, agents that increase transcription of caspase-3 protease could reinforce cell death via CPP32-mediated apoptosis. In this regard, genistein may find an application in the treatment of human prostate carcinoma, independently of hormone sensitivity. (C) 2000 Editions scientifiques et medicales Elsevier SAS.