In Vitro Suppression of Growth of Murine WEHI-3 Leukemia Cells and in Vivo Promotion of Phagocytosis in a Leukemia Mice Model by Indole-3-carbinol
In Vitro Suppression of Growth of Murine WEHI-3 Leukemia Cells and in Vivo Promotion of Phagocytosis in a Leukemia Mice Model by Indole-3-carbinol
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DOI：
10.1021/jf300963t
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发表时间：
2012-08-08
影响因子：
6.1
通讯作者：
Chung, Jing-Gung
中科院分区：
文献类型：
--
作者：
Lu, Hsu-Feng;Tung, Wei-Lin;Chung, Jing-Gung
吲哚-3-甲醇（Indole-3-carbinol，I3 C）是一种潜在的抗癌物质，存在于十字花科蔬菜中，主要存在于花椰菜和大白菜中。然而，I3 C对小鼠白血病WEHI-3细胞的凋亡作用和对白血病小鼠模型的免疫应答的促进作用的生物活性尚不清楚。在这项研究中，我们研究了I3 C在体外对细胞周期阻滞和凋亡以及体内免疫调节的影响。I3 C降低了WEHI-3细胞的存活率，并以浓度和时间依赖性方式引起形态学变化。I3 C还导致G 0/G1期阻滞，降低细胞周期蛋白A、细胞周期蛋白D和CDK 2的水平，并增加p21（WAF 1/CIP 1）的水平。流式细胞仪分析进一步证明I3 C促进WEHI-3细胞中ROS和细胞内Ca 2+的产生，并降低Delta Psi（m）的水平。暴露于I3 C 24 h后的细胞显示DNA断裂和染色质凝聚。彗星试验也表明，I3 C诱导受检细胞的DNA损伤。I3 C增加细胞色素c、FADD、GADD 153、GRP 78和半胱天冬酶-12的水平，并诱导半胱天冬酶-3、-8和-9的活性。此外，如EMSA和Western印迹分析所示，I3 C减弱了13 C处理的WEHI-3细胞中NF-κ B DNA结合活性。在体内研究中，我们研究了I3 C对WEHI-3白血病小鼠的影响。结果表明，I3 C可增加T细胞水平，降低巨噬细胞水平。I3 C还降低了肝脏和脾脏的重量，并且与未处理的白血病小鼠组相比，它促进了巨噬细胞的吞噬作用。根据我们的研究结果，I3 C影响小鼠白血病WEHI-3细胞在体外和体内。
Indole-3-carbinol (I3C), a potential anticancer substance, can be found in cruciferous (cabbage family) vegetables, mainly cauliflower and Chinese cabbage. However, the bioactivity of I3C on the apoptotic effects of murine leukemia WEHI-3 cells and promotion of immune responses in leukemia mice model are unclear. In this study, we investigated the effect of I3C on cell-cycle arrest and apoptosis in vitro and immunomodulation in vivo. I3C decreased the viable WEHI-3 cells and caused morphological changes in a concentration- and time-dependent manner. I3C also led to G0/G1 phase arrest, decreased the levels of cyclin A, cyclin D, and CDK2, and increased the level of p21(WAF1/CIP1). Flow cytometric analyses further proved that I3C promoted ROS and intracellular Ca2+ production and decreased the levels of Delta Psi(m), in WEHI-3 cells. Cells after exposure to I3C for 24 h showed DNA fragmentation and chromatin condensation. Comet assay also indicated that I3C induced DNA damage in examined cells. I3C increased the levels of cytochrome c, FADD, GADD153, GRP78, and caspase-12 as well as induced activities of caspase-3, -8, and -9. Moreover, I3C attenuated NF-kappa B DNA binding activity in 13C-treated WEHI-3 cells as shown by EMSA and Western blotting analyses. In the in vivo study, we examined the effects of I3C on WEHI-3 leukemia mice. Results showed that I3C increased the level of T cells and decreased the level of macrophages. I3C also reduced the weights of liver and spleen, and it promoted phagocytosis by macrophages as compared to the nontreated leukemia mice group. On the basis of our results, I3C affects murine leukemia WEHI-3 cells both in vitro and in vivo.