Critical role for reactive oxygen species in apoptosis induction and cell migration inhibition by diallyl trisulfide, a cancer chemopreventive component of garlic.
Critical role for reactive oxygen species in apoptosis induction and cell migration inhibition by diallyl trisulfide, a cancer chemopreventive component of garlic.
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DOI：
10.1007/s10549-013-2440-2
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发表时间：
2013-02
影响因子：
3.8
通讯作者：
Singh, Shivendra V.
中科院分区：
文献类型：
--
作者：
Chandra-Kuntal, Kumar;Lee, Joomin;Singh, Shivendra V.
二烯丙基三硫化物（DATS）是一种结构简单但具有生物活性的加工大蒜成分，在实验啮齿动物中具有抗化学诱导和致癌基因驱动的癌症的体内活性。本研究以人乳腺癌细胞为模型，对DATS的抗癌作用机制提供了新的见解。将人乳腺癌细胞（分别为MCF-7和MDA-MB-231）和源自转基因小鼠（BRI-JM 04）自发发生乳腺肿瘤的细胞系暴露于DATS导致细胞活力的剂量依赖性抑制，并伴有凋亡诱导。一种非致瘤性正常人乳腺细胞系（MCF-10A）对DATS的生长抑制和凋亡诱导具有抗性。在MDA-MB-231、MCF-7和BRI-JM 04细胞中，DATS诱导的凋亡与活性氧（ROS）的产生相关，如通过荧光显微镜和使用化学探针（MitoSOX Red）的流式细胞术所证明的。在MDA-MB-231和MCF-7细胞中，过表达Cu，Zn-SOD和Mn-SOD可显著抑制DAT诱导的ROS产生和细胞凋亡。过表达Mn-SOD可明显抑制DATS处理引起的巴克的活化，但不抑制Bax的活化。在MCF-10A细胞中，DATS处理引起ROS产生，但不激活Bax或巴克。此外，与参与上皮-间充质转化的蛋白质水平变化相关的Cu、Zn-SOD和Mn-SOD过表达部分但显着减弱了DATS介导的细胞迁移抑制作用。过表达Mn-SOD可部分减弱DAT介导的血红素氧合酶-1诱导作用。这些结果提供了新的机制的见解，表明ROS在DATS的抗癌作用中的关键作用。
Diallyl trisulfide (DATS) is a structurally simple but biologically active constituent of processed garlic with in vivo activity against chemically-induced as well as oncogene-driven cancer in experimental rodents. The present study offers novel insights into the mechanisms underlying anticancer effects of DATS using human breast cancer cells as a model. Exposure of human breast cancer cells (MCF-7 and MDA-MB-231, respectively) and a cell line derived from spontaneously developing mammary tumor of a transgenic mouse (BRI-JM04) to DATS resulted in a dose-dependent inhibition of cell viability that was accompanied by apoptosis induction. A non-tumorigenic normal human mammary cell line (MCF-10A) was resistant to growth inhibition and apoptosis induction by DATS. The DATS-induced apoptosis in MDA-MB-231, MCF-7, and BRI-JM04 cells was associated with reactive oxygen species (ROS) production as evidenced by fluorescence microscopy and flow cytometry using a chemical probe (MitoSOX Red). Overexpression of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) as well as Mn-SOD conferred significant protection against DATS-induced ROS production and apoptotic cell death in MDA-MB-231 and MCF-7 cells. Activation of Bak, but not Bax, resulting from DATS treatment was markedly suppressed by overexpression of Mn-SOD. The DATS treatment caused ROS generation, but not activation of Bax or Bak, in MCF-10A cells. Furthermore, the DATS-mediated inhibition of cell migration was partially but significantly attenuated by Cu,Zn-SOD and Mn-SOD overexpression in association with changes in levels of proteins involved in epithelial-mesenchymal transition. The DATS-mediated induction of heme oxygenase-1 was partially attenuated by overexpression of Mn-SOD. These results provide novel mechanistic insights indicating a critical role for ROS in anticancer effects of DATS.
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DOI：
10.1186/bcr2416
发表时间：
2009
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Tomaskovic-Crook E;Thompson EW;Thiery JP
通讯作者：
Thiery JP
影响因子：
11.2
作者：
Antosiewicz, Jedrzej;Herman-Antosiewicz, Anna;Singh, Shivendra V.
通讯作者：
Singh, Shivendra V.
影响因子：
19
作者：
Hurd TR;DeGennaro M;Lehmann R
通讯作者：
Lehmann R
影响因子：
5
作者：
Sielicka-Dudzin, Alicja;Borkowska, Andzelika;Antosiewicz, Jedrzej
通讯作者：
Antosiewicz, Jedrzej
影响因子：
7.4
作者：
Chen, C;Pung, D;Kong, ANT
通讯作者：
Kong, ANT