Sulforaphane Inhibits Liver Cancer Cell Growth and Angiogenesis

Shinya Sato, K. Moriya, Masanori Furukawa, Soichiro Saikawa, T. Namisaki, Mitsuteru Kitade, H. Kawaratani, K. Kaji, Hiroaki Takaya, Naotaka Shimozato, Yasuhiko Sawada, K. Seki, K. Kitagawa, Takemi Akahane, A. Mitoro, Yasushi Okura, H. Yoshiji, J. Yamao
{"title":"Sulforaphane Inhibits Liver Cancer Cell Growth and Angiogenesis","authors":"Shinya Sato, K. Moriya, Masanori Furukawa, Soichiro Saikawa, T. Namisaki, Mitsuteru Kitade, H. Kawaratani, K. Kaji, Hiroaki Takaya, Naotaka Shimozato, Yasuhiko Sawada, K. Seki, K. Kitagawa, Takemi Akahane, A. Mitoro, Yasushi Okura, H. Yoshiji, J. Yamao","doi":"10.21767/2254-6081.100189","DOIUrl":null,"url":null,"abstract":"Sulforaphane (SFN) exhibits inhibitory effects in different types of cancers. However, its inhibitory effect on liver cancer remains unknown. This study aimed to determine the therapeutic potential of SFN for the treatment of liver cancer and explore the functional mechanisms underlying the inhibitory effects of SFN. Water-Soluble Tetrazolium salt (WST-1) assay was performed to assess the in vitro effect of SFN on cell proliferation in the human liver cancer cell lines, HepG2 and Huh-7. The mRNA levels of Nrf2 target genes and cell cycle-related genes were determined using quantitative RT-PCR. For assessing the inhibitory effect of SFN in vivo, we injected immortalized liver cancer cells into BALB/c nude mice as a xenograft model. SFN was orally administrated daily after tumor inoculation and continued for thirty-five days until their sacrifices. Nrf2 activation, induced by SFN, was confirmed by mRNA upregulation of HO-1, MRP2, and NQO1 in both the cell lines. Significant inhibition of liver cancer cell proliferation by SFN was shown in vitro in a dose-dependent manner by the downregulation of CCND1, CCNB1, CDK1 and CDK2. In in vivo studies, the administration of SFN significantly reduced the subcutaneous tumor burdens at the end of experiments by suppressing tumor cell proliferation, confirmed by Ki67 immunohistochemical analysis. The mRNA levels of CCND1, CCNB1, CDK1 and CDK2 were also decreased in these SFNtreated xenograft tumors. Moreover, CD34 immunostaining elucidated that the intratumoral neovascularization was markedly attenuated in the SFN-treated xenograft tumors. SFN exerts inhibitory effect on human liver cancer cells with antiangiogenic activity. The earlier version of this study was presented at the meeting of AASLD Liver Learning on Oct 2017.","PeriodicalId":91204,"journal":{"name":"Archives in cancer research","volume":"6 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.21767/2254-6081.100189","citationCount":"7","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives in cancer research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.21767/2254-6081.100189","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 7

Abstract

Sulforaphane (SFN) exhibits inhibitory effects in different types of cancers. However, its inhibitory effect on liver cancer remains unknown. This study aimed to determine the therapeutic potential of SFN for the treatment of liver cancer and explore the functional mechanisms underlying the inhibitory effects of SFN. Water-Soluble Tetrazolium salt (WST-1) assay was performed to assess the in vitro effect of SFN on cell proliferation in the human liver cancer cell lines, HepG2 and Huh-7. The mRNA levels of Nrf2 target genes and cell cycle-related genes were determined using quantitative RT-PCR. For assessing the inhibitory effect of SFN in vivo, we injected immortalized liver cancer cells into BALB/c nude mice as a xenograft model. SFN was orally administrated daily after tumor inoculation and continued for thirty-five days until their sacrifices. Nrf2 activation, induced by SFN, was confirmed by mRNA upregulation of HO-1, MRP2, and NQO1 in both the cell lines. Significant inhibition of liver cancer cell proliferation by SFN was shown in vitro in a dose-dependent manner by the downregulation of CCND1, CCNB1, CDK1 and CDK2. In in vivo studies, the administration of SFN significantly reduced the subcutaneous tumor burdens at the end of experiments by suppressing tumor cell proliferation, confirmed by Ki67 immunohistochemical analysis. The mRNA levels of CCND1, CCNB1, CDK1 and CDK2 were also decreased in these SFNtreated xenograft tumors. Moreover, CD34 immunostaining elucidated that the intratumoral neovascularization was markedly attenuated in the SFN-treated xenograft tumors. SFN exerts inhibitory effect on human liver cancer cells with antiangiogenic activity. The earlier version of this study was presented at the meeting of AASLD Liver Learning on Oct 2017.
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
萝卜硫素抑制肝癌细胞生长和血管生成
萝卜硫素(SFN)在不同类型的癌症中表现出抑制作用。然而,其对肝癌的抑制作用尚不清楚。本研究旨在确定SFN对肝癌的治疗潜力,并探讨SFN抑制作用的作用机制。采用水溶四唑盐(WST-1)实验,观察SFN对人肝癌细胞株HepG2和Huh-7细胞增殖的影响。采用定量RT-PCR检测Nrf2靶基因和细胞周期相关基因的mRNA水平。为了评估SFN在体内的抑制作用,我们将永生化的肝癌细胞注射到BALB/c裸鼠体内作为异种移植模型。肿瘤接种后每天口服SFN,持续35天,直至死亡。在两种细胞系中,HO-1、MRP2和NQO1 mRNA的上调证实了SFN诱导的Nrf2激活。通过下调CCND1、CCNB1、CDK1和CDK2, SFN在体外以剂量依赖性方式显著抑制肝癌细胞增殖。在体内研究中,Ki67免疫组织化学分析证实,SFN通过抑制肿瘤细胞增殖,在实验结束时显著减轻了皮下肿瘤负荷。CCND1、CCNB1、CDK1和CDK2的mRNA水平在sfn治疗的异种移植肿瘤中也有所降低。此外,CD34免疫染色表明sfn治疗的异种移植肿瘤瘤内新生血管明显减弱。SFN对人肝癌细胞有抑制作用,具有抗血管生成活性。该研究的早期版本于2017年10月在AASLD肝脏学习会议上发表。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
自引率
0.00%
发文量
0
期刊最新文献
Novel Strategy for Colorectal Liver Cancer- Hepatocyte Growth Factor EstimationConcept Multimodality Imaging Based Treatment Volume Definition for Reirradiation of Recurrent Small Cell Lung Cancer (SCLC) Evaluation of Antimicrobial and Anticancer Activity of Lactococcus garvieae Derived Bacteriocin Clinical Challenges to Current Molecularly Targeted Therapies in CellularBreakdown in the Lungs Cellular breakdown in the lungs: Brief Report of Advanced and TraditionalTreatments and Diagnosis
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1