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吲哚-3-甲醇通过激活凋亡信号通路抑制结直肠癌细胞 LoVo 的增殖。

Indole-3-carbinol inhibits the proliferation of colorectal carcinoma LoVo cells through activation of the apoptotic signaling pathway.

机构信息

Department of Biological Science, 65440Gachon University, Sujeong-gu, Seongnam-si, Gyeonggi-do, Republic of Korea.

Department of Bio&Chemical Engineering, 65686Hongik University, Jochiwon-eup, Sejong-si, Republic of Korea.

出版信息

Hum Exp Toxicol. 2021 Dec;40(12):2099-2112. doi: 10.1177/09603271211021475. Epub 2021 Jun 4.

DOI:10.1177/09603271211021475
PMID:34085558
Abstract

Indole-3-carbinol (I3C) is a phytochemical that exhibits growth-inhibitory activity against various cancer cells. However, there are limited studies on the effects of I3C on colon cancer cells. In this study, the growth-inhibitory activity of I3C against the human colorectal carcinoma cell line (LoVo) was examined. The results of the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide, colony formation, and cell counting assays revealed that I3C suppressed the proliferation of LoVo cells. Microscopy and wound-healing analyses revealed that I3C affected the morphology and inhibited the migration of LoVo cells, respectively. I3C induced apoptosis and DNA fragmentation as evidenced by the results of fluorescein isothiocyanate-conjugated annexin V staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling assay, respectively. Additionally, I3C arrested the cell cycle at the G0/G1 phase and enhanced the reactive oxygen species levels. Western blotting analysis revealed that treatment with I3C resulted in the activation of apoptotic proteins, such as poly(ADP-ribose) polymerase, caspase-3, caspase-7, caspase-9, Bax, Bim, and p53 in LoVo cells. These results indicate that I3C induces apoptosis in LoVo cells by upregulating p53, leading to the activation of Bax and caspases. Taken together, I3C exerts cytotoxic effects on LoVo cells by activating apoptosis.

摘要

吲哚-3-甲醇(I3C)是一种植物化学物质,对各种癌细胞表现出生长抑制活性。然而,关于 I3C 对结肠癌细胞的影响的研究有限。在这项研究中,研究了 I3C 对人结肠直肠癌细胞系(LoVo)的生长抑制活性。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴化物、集落形成和细胞计数测定的结果表明,I3C 抑制了 LoVo 细胞的增殖。显微镜和划痕愈合分析分别显示 I3C 影响细胞形态并抑制 LoVo 细胞的迁移。碘化丙啶(PI)荧光染色和末端脱氧核苷酸转移酶介导的 dUTP 生物素缺口末端标记(TUNEL)实验结果表明,I3C 诱导细胞凋亡和 DNA 片段化。此外,I3C 将细胞周期阻滞在 G0/G1 期,并增加活性氧(ROS)水平。Western blot 分析显示,I3C 处理导致凋亡蛋白如多聚(ADP-核糖)聚合酶、caspase-3、caspase-7、caspase-9、Bax、Bim 和 p53 在 LoVo 细胞中激活。这些结果表明,I3C 通过上调 p53 诱导 LoVo 细胞凋亡,从而激活 Bax 和 Caspases。总之,I3C 通过激活细胞凋亡对 LoVo 细胞发挥细胞毒性作用。

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