丙烯基异硫氰酸酯对 7,12-二甲基苯并（a）蒽和 N-甲基-N-亚硝脲诱导的乳腺肿瘤发生中 NF-κB 信号的影响。
Effect of allyl isothiocyanate on NF-κB signaling in 7,12-dimethylbenz(a)anthracene and N-methyl-N-nitrosourea-induced mammary carcinogenesis.
机构信息
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, 608 002, India.
Center of Advanced Studies in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai, 600 025, Tamil Nadu, India.
出版信息
Breast Cancer. 2018 Jan;25(1):50-59. doi: 10.1007/s12282-017-0783-y. Epub 2017 May 13.
BACKGROUND
Inflammation plays a pivotal role in the process of carcinogenesis and phytochemicals have anti-inflammatory properties gaining more importance in cancer chemoprevention. The present study aimed to investigate the anti-inflammatory effect of allyl isothiocyanate (AITC) on 7,12-dimethylbenz(a)anthracene (DMBA)- and N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis in female Sprague-Dawley rats.
METHODS
RT-PCR and western blot analysis showed that inflammatory markers such as NF-κB p65, TNF-α, and IL-6 were overexpressed in mammary tumor tissues. Histological analysis of tumor tissues shows abnormality in hematoxylin and eosin (H&E) staining and toluidine blue (TB) staining of mast cell content, and lipid accumulation in oil red O staining.
RESULTS
Administration of AITC (20 mg/kg bw) to carcinogen-injected rats significantly decreased the expression of NF-κB p65, TNF-α, and IL-6 in mammary tissues. Further, molecular docking study demonstrates the binding of AITC to NF-κB p65. Remarkably, AITC treatments control the growth of cancer cells as clearly evidenced by histopathological analysis. Staining of mammary tissues for mast cells and lipids indicates that AITC treatment to carcinogen-administrated rats significantly reduced mammary tumorigenesis.
CONCLUSIONS
The result suggests that AITC has anti-inflammatory potential to prevent DMBA- and MNU-induced mammary carcinogenesis in rats.
背景
炎症在致癌过程中起着关键作用，植物化学物质具有抗炎特性，在癌症化学预防中越来越受到重视。本研究旨在探讨丙烯基异硫氰酸酯（AITC）对 7,12-二甲基苯并（a）蒽（DMBA）和 N-甲基-N-亚硝基脲（MNU）诱导的雌性 Sprague-Dawley 大鼠乳腺致癌作用的抗炎作用。
方法
RT-PCR 和 Western blot 分析显示，炎症标志物如 NF-κB p65、TNF-α 和 IL-6 在乳腺肿瘤组织中过度表达。肿瘤组织的组织学分析显示苏木精和伊红（H&E）染色以及甲苯胺蓝（TB）染色的肥大细胞含量以及油红 O 染色的脂质积累存在异常。
结果
给予 AITC（20mg/kg bw）可显著降低致癌剂注射大鼠乳腺组织中 NF-κB p65、TNF-α 和 IL-6 的表达。此外，分子对接研究表明 AITC 与 NF-κB p65 结合。值得注意的是，AITC 治疗明显控制了癌细胞的生长，这一点从组织病理学分析中可以清楚地看出。对乳腺组织进行肥大细胞和脂质染色表明，AITC 治疗可显著减少致癌剂处理大鼠的乳腺肿瘤形成。
结论
结果表明 AITC 具有抗炎潜力，可预防 DMBA 和 MNU 诱导的大鼠乳腺致癌作用。
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