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二烯丙基三硫醚衍生物对人前列腺癌细胞 PC-3 凋亡的诱导作用。

Effect of diallyl trisulfide derivatives on the induction of apoptosis in human prostate cancer PC-3 cells.

机构信息

College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.

出版信息

Mol Cell Biochem. 2012 Apr;363(1-2):75-84. doi: 10.1007/s11010-011-1159-9. Epub 2011 Dec 6.

DOI:10.1007/s11010-011-1159-9
PMID:22143535
Abstract

The effects of five derivatives of diallyl trisulfide (DATS) were investigated on apoptosis in prostate cancer PC-3 cells, including dibutenyl trisulfide (DBTS), bis(2-methylallyl) trisulfide (2-M-DATS), dipentenyl trisulfide (DPTS), bis(3-methylbut-2-enyl) trisulfide (3-M-DBTS), and dihexenyl trisulfide (DHTS). Our present study demonstrated that DATS derivatives can suppress proliferation of PC-3 cells in a dose- and time-dependent manner, and that a change in the DATS structure could have an impact on its biological activity in the following order: 2-M-DATS > DBTS ≈ DPTS ≈ DATS > 3-M-DBTS ≈ DHTS. Typical apoptotic nuclei were shown by Hoechst 33342 staining with 80 μM concentrations of DATS derivatives for 24 h. And flow cytometric analysis and DNA fragmentation assay also demonstrated that DATS derivatives induced apoptosis in PC-3 cells. Meanwhile, experimental results showed that DBTS, 2-M-DATS, and DPTS cause G2-M phase cell cycle arrest. Furthermore, a series of apoptosis-associated features were observed, which include a notable decrease in the expression of procaspases-3, up-regulation of pro-apoptotic proteins Bax expression, and down-regulation of anti-apoptotic proteins Bcl-2 expression in PC-3 cells. All of the evidences above indicate that DATS derivatives suppressed proliferation of PC-3 cells which was associated with the induction of apoptosis regulated by Bax/Bcl-2.

摘要

五种二烯丙基三硫醚(DATS)衍生物对前列腺癌细胞 PC-3 细胞凋亡的影响进行了研究,包括二丁烯基三硫醚(DBTS)、双(2-甲基烯丙基)三硫醚(2-M-DATS)、二戊烯基三硫醚(DPTS)、双(3-甲基-2-丁烯基)三硫醚(3-M-DBTS)和二己烯基三硫醚(DHTS)。本研究表明,DATS 衍生物可以剂量和时间依赖的方式抑制 PC-3 细胞的增殖,并且 DATS 结构的变化可能会对其生物活性产生以下影响:2-M-DATS > DBTS ≈ DPTS ≈ DATS > 3-M-DBTS ≈ DHTS。用 80 μM 浓度的 DATS 衍生物处理 24 h 后,通过 Hoechst 33342 染色显示出典型的凋亡核。流式细胞术分析和 DNA 片段化分析也表明 DATS 衍生物诱导 PC-3 细胞凋亡。同时,实验结果表明 DBTS、2-M-DATS 和 DPTS 导致细胞周期 G2-M 期阻滞。此外,观察到一系列与凋亡相关的特征,包括 PC-3 细胞中前半胱氨酸蛋白酶-3 的表达显著降低,促凋亡蛋白 Bax 的表达上调,以及抗凋亡蛋白 Bcl-2 的表达下调。所有这些证据表明,DATS 衍生物抑制了 PC-3 细胞的增殖,这与 Bax/Bcl-2 调控的凋亡诱导有关。

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