• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

硫代珊瑚素改变神经内分泌表型并激活 MTC-TT 细胞系中的 Notch 通路。

Thiocoraline alters neuroendocrine phenotype and activates the Notch pathway in MTC-TT cell line.

机构信息

University of Wisconsin Medical School, Madison, Wisconsin.

出版信息

Cancer Med. 2013 Oct;2(5):734-43. doi: 10.1002/cam4.118. Epub 2013 Sep 17.

DOI:10.1002/cam4.118
PMID:24403239
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3892805/
Abstract

Medullary thyroid cancer (MTC) is an aggressive neuroendocrine tumor (NET). Previous research has shown that activation of Notch signaling has a tumor suppressor role in NETs. The potential therapeutic effect of thiocoraline on the activation of the Notch pathway in an MTC cell line (TT) was investigated. Thiocoraline was isolated from a marine bacterium Verrucosispora sp. MTT assay (3-[4, 5-dimethylthiazole-2-yl]-2, 5-diphenyltetrazolium bromide) was used to determine the IC50 value and to measure cell proliferation. Western blot revealed the expression of Notch isoforms, NET, and cell cycle markers. Cell cycle progression was validated by flow cytometry. The mRNA expression of Notch isoforms and downstream targets were measured using real-time PCR. The IC50 value for thiocoraline treatment in TT cells was determined to be 7.6 nmol/L. Thiocoraline treatment decreased cell proliferation in a dose- and time-dependent manner. The mechanism of growth inhibition was found to be cell cycle arrest in G1 phase. Thiocoraline activated the Notch pathway as demonstrated by the dose-dependent increase in mRNA and protein expression of Notch isoforms. Furthermore, treatment with thiocoraline resulted in changes in the expression of downstream targets of the Notch pathway (HES1, HES2, HES6, HEY1, and HEY2) and reduced expression of NET markers, CgA, and ASCL1. Thiocoraline is a potent Notch pathway activator and an inhibitor of MTC-TT cell proliferation at low nanomolar concentrations. These results provide exciting evidence for the use of thiocoraline as a potential treatment for intractable MTC.

摘要

甲状腺髓样癌 (MTC) 是一种侵袭性神经内分泌肿瘤 (NET)。先前的研究表明，Notch 信号通路的激活在 NET 中具有肿瘤抑制作用。本研究旨在探讨硫代珊瑚素对 MTC 细胞系 (TT) Notch 通路激活的潜在治疗作用。硫代珊瑚素从海洋细菌 Verrucosispora sp. 中分离得到。噻唑蓝 (MTT) 法用于测定 IC50 值和细胞增殖。Western blot 检测 Notch 同工型、NET 和细胞周期标志物的表达。通过流式细胞术验证细胞周期进程。使用实时 PCR 测量 Notch 同工型和下游靶标 mRNA 的表达。TT 细胞中硫代珊瑚素的 IC50 值为 7.6 nmol/L。硫代珊瑚素处理呈剂量和时间依赖性地降低细胞增殖。生长抑制的机制被发现是 G1 期细胞周期停滞。硫代珊瑚素激活 Notch 通路，表现为 Notch 同工型的 mRNA 和蛋白表达呈剂量依赖性增加。此外，硫代珊瑚素处理导致 Notch 通路下游靶标 (HES1、HES2、HES6、HEY1 和 HEY2) 的表达发生变化，NET 标志物 CgA 和 ASCL1 的表达降低。硫代珊瑚素是一种有效的 Notch 通路激活剂，可在低纳摩尔浓度下抑制 MTC-TT 细胞增殖。这些结果为使用硫代珊瑚素作为治疗难治性 MTC 的潜在方法提供了令人兴奋的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5494/3892805/45ce5db98b8c/cam40002-0734-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5494/3892805/9bbc1f3ea347/cam40002-0734-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5494/3892805/a8a4e13116b9/cam40002-0734-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5494/3892805/57e10a308ab9/cam40002-0734-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5494/3892805/7fd290a903c2/cam40002-0734-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5494/3892805/92e2bd74ad61/cam40002-0734-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5494/3892805/45ce5db98b8c/cam40002-0734-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5494/3892805/9bbc1f3ea347/cam40002-0734-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5494/3892805/a8a4e13116b9/cam40002-0734-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5494/3892805/57e10a308ab9/cam40002-0734-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5494/3892805/7fd290a903c2/cam40002-0734-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5494/3892805/92e2bd74ad61/cam40002-0734-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5494/3892805/45ce5db98b8c/cam40002-0734-f6.jpg

相似文献

1
Thiocoraline alters neuroendocrine phenotype and activates the Notch pathway in MTC-TT cell line.硫代珊瑚素改变神经内分泌表型并激活 MTC-TT 细胞系中的 Notch 通路。
Cancer Med. 2013 Oct;2(5):734-43. doi: 10.1002/cam4.118. Epub 2013 Sep 17.
2
Thiocoraline activates the Notch pathway in carcinoids and reduces tumor progression in vivo.硫代珊瑚菌素激活类癌中的Notch信号通路并在体内减少肿瘤进展。
Cancer Gene Ther. 2014 Dec;21(12):518-25. doi: 10.1038/cgt.2014.57. Epub 2014 Nov 21.
3
Overexpression of the NOTCH1 intracellular domain inhibits cell proliferation and alters the neuroendocrine phenotype of medullary thyroid cancer cells.NOTCH1细胞内结构域的过表达抑制细胞增殖并改变甲状腺髓样癌细胞的神经内分泌表型。
J Biol Chem. 2006 Dec 29;281(52):39819-30. doi: 10.1074/jbc.M603578200. Epub 2006 Nov 7.
4
MiR-182 promotes cancer invasion by linking RET oncogene activated NF-κB to loss of the HES1/Notch1 regulatory circuit.微小RNA-182通过将RET致癌基因激活的核因子κB与HES1/Notch1调控回路的缺失相联系来促进癌症侵袭。
Mol Cancer. 2017 Jan 26;16(1):24. doi: 10.1186/s12943-016-0563-x.
5
Suberoyl bis-hydroxamic acid activates Notch-1 signaling and induces apoptosis in medullary thyroid carcinoma cells.辛二酰双羟肟酸激活Notch-1信号通路并诱导甲状腺髓样癌细胞凋亡。
Oncologist. 2008 Feb;13(2):98-104. doi: 10.1634/theoncologist.2007-0190.
6
Resveratrol induces Notch2-mediated apoptosis and suppression of neuroendocrine markers in medullary thyroid cancer.白藜芦醇诱导神经内分泌标志物在甲状腺髓样癌中 Notch2 介导的细胞凋亡和抑制。
Ann Surg Oncol. 2011 May;18(5):1506-11. doi: 10.1245/s10434-010-1488-z. Epub 2010 Dec 24.
7
Antisurvivin oligonucleotides inhibit growth and induce apoptosis in human medullary thyroid carcinoma cells.抗生存素寡核苷酸抑制人甲状腺髓样癌细胞生长并诱导其凋亡。
Exp Mol Med. 2006 Jun 30;38(3):230-40. doi: 10.1038/emm.2006.28.
8
Expression of the active Notch1 decreases MTC tumor growth in vivo.活跃的 Notch1 的表达会降低体内 MTC 肿瘤的生长。
J Surg Res. 2011 Nov;171(1):23-7. doi: 10.1016/j.jss.2011.03.035. Epub 2011 Apr 13.
9
Salinomycin and its derivatives as potent RET transcriptional inhibitors for the treatment of medullary thyroid carcinoma.黏菌素及其衍生物作为有效的 RET 转录抑制剂，用于治疗甲状腺髓样癌。
Int J Oncol. 2020 Jan;56(1):348-358. doi: 10.3892/ijo.2019.4916. Epub 2019 Nov 20.
10
Anti-proliferative and anti-invasive effects of ferulic acid in TT medullary thyroid cancer cells interacting with URG4/URGCP.阿魏酸在与URG4/URGCP相互作用的TT甲状腺髓样癌细胞中的抗增殖和抗侵袭作用
Tumour Biol. 2016 Feb;37(2):1933-40. doi: 10.1007/s13277-015-3984-z. Epub 2015 Sep 3.

引用本文的文献

1
The role of MAPK, notch and Wnt signaling pathways in papillary thyroid cancer: Evidence from a systematic review and meta-analyzing microarray datasets employing bioinformatics knowledge and literature.丝裂原活化蛋白激酶（MAPK）、Notch和Wnt信号通路在甲状腺乳头状癌中的作用：基于运用生物信息学知识和文献对微阵列数据集进行系统评价和荟萃分析的证据
Biochem Biophys Rep. 2023 Dec 14;37:101606. doi: 10.1016/j.bbrep.2023.101606. eCollection 2024 Mar.
2
Natural Cyclopeptides as Anticancer Agents in the Last 20 Years.近 20 年来天然环肽类化合物作为抗癌药物的研究进展
Int J Mol Sci. 2021 Apr 12;22(8):3973. doi: 10.3390/ijms22083973.
3
Notch Signaling in Thyroid Cancer.

本文引用的文献

1
Heterogeneity of breast cancer stem cells as evidenced with Notch-dependent and Notch-independent populations.乳腺癌干细胞的异质性表现为 Notch 依赖性和 Notch 非依赖性群体。
Cancer Med. 2012 Oct;1(2):105-13. doi: 10.1002/cam4.18. Epub 2012 Jul 18.
2
Molecular pathology and genetics of pancreatic endocrine tumours.胰腺内分泌肿瘤的分子病理学和遗传学。
J Mol Endocrinol. 2012 Jun 26;49(1):R37-50. doi: 10.1530/JME-12-0069. Print 2012 Aug.
3
Role of vandetanib in the management of medullary thyroid cancer.凡德他尼在甲状腺髓样癌治疗中的作用。
Notch 信号通路在甲状腺癌中的作用。
Adv Exp Med Biol. 2021;1287:155-168. doi: 10.1007/978-3-030-55031-8_10.
4
Thiocoraline mediates drug resistance in MCF-7 cells via PI3K/Akt/BCRP signaling pathway.硫代珊瑚素通过PI3K/Akt/BCRP信号通路介导MCF-7细胞的耐药性。
Cytotechnology. 2019 Feb;71(1):401-409. doi: 10.1007/s10616-019-00301-w. Epub 2019 Jan 28.
5
Histone deacetylase inhibitor thailandepsin-A activates Notch signaling and suppresses neuroendocrine cancer cell growth .组蛋白去乙酰化酶抑制剂泰国辛-A激活Notch信号通路并抑制神经内分泌癌细胞生长。
Oncotarget. 2017 Aug 7;8(41):70828-70840. doi: 10.18632/oncotarget.19993. eCollection 2017 Sep 19.
6
Antineoplastic effects of histone deacetylase inhibitors in neuroendocrine cancer cells are mediated through transcriptional regulation of Notch1 by activator protein 1.组蛋白去乙酰化酶抑制剂在神经内分泌癌细胞中的抗肿瘤作用是通过激活蛋白 1 对 Notch1 的转录调控来介导的。
Cancer Med. 2017 Sep;6(9):2142-2152. doi: 10.1002/cam4.1151. Epub 2017 Aug 4.
7
Tumor-suppressor role of Notch3 in medullary thyroid carcinoma revealed by genetic and pharmacological induction.遗传和药理学诱导揭示Notch3在甲状腺髓样癌中的肿瘤抑制作用
Mol Cancer Ther. 2015 Feb;14(2):499-512. doi: 10.1158/1535-7163.MCT-14-0073. Epub 2014 Dec 15.
8
Thiocoraline activates the Notch pathway in carcinoids and reduces tumor progression in vivo.硫代珊瑚菌素激活类癌中的Notch信号通路并在体内减少肿瘤进展。
Cancer Gene Ther. 2014 Dec;21(12):518-25. doi: 10.1038/cgt.2014.57. Epub 2014 Nov 21.
9
Biosynthetic modularity rules in the bisintercalator family of antitumor compounds.抗肿瘤化合物双嵌入剂家族中的生物合成模块化规则。
Mar Drugs. 2014 May 9;12(5):2668-99. doi: 10.3390/md12052668.
Biologics. 2012;6:59-66. doi: 10.2147/BTT.S24220. Epub 2012 Mar 8.
4
Noncanonical Hedgehog signaling.非经典 Hedgehog 信号通路。
Vitam Horm. 2012;88:55-72. doi: 10.1016/B978-0-12-394622-5.00003-1.
5
First natural analogs of the cytotoxic thiodepsipeptide thiocoraline A from a marine Verrucosispora sp.海洋 Verrucosispora sp. 来源的细胞毒性硫代二肽硫考来宁 A 的首个天然类似物
J Org Chem. 2011 Aug 19;76(16):6542-7. doi: 10.1021/jo200661n. Epub 2011 Jul 20.
6
Human achaete-scute homolog-1 is highly expressed in a subset of neuroendocrine tumors.人类无翅型MMTV整合位点家族成员1在一部分神经内分泌肿瘤中高表达。
Oncol Rep. 1997 Jul-Aug;4(4):775-8. doi: 10.3892/or.4.4.775.
7
Expression of the active Notch1 decreases MTC tumor growth in vivo.活跃的 Notch1 的表达会降低体内 MTC 肿瘤的生长。
J Surg Res. 2011 Nov;171(1):23-7. doi: 10.1016/j.jss.2011.03.035. Epub 2011 Apr 13.
8
Expression of Notch receptors, ligands, and target genes during development of the mouse mammary gland.Notch 受体、配体和靶基因在小鼠乳腺发育过程中的表达。
J Cell Physiol. 2011 Jul;226(7):1940-52. doi: 10.1002/jcp.22526.
9
Hesperetin, a potential therapy for carcinoid cancer.橙皮素，一种用于类癌肿瘤治疗的潜在药物。
Am J Surg. 2011 Mar;201(3):329-32; discussion 333. doi: 10.1016/j.amjsurg.2010.08.018.
10
Resveratrol induces Notch2-mediated apoptosis and suppression of neuroendocrine markers in medullary thyroid cancer.白藜芦醇诱导神经内分泌标志物在甲状腺髓样癌中 Notch2 介导的细胞凋亡和抑制。
Ann Surg Oncol. 2011 May;18(5):1506-11. doi: 10.1245/s10434-010-1488-z. Epub 2010 Dec 24.