PUBLICATION

Cryptotanshinone, a novel tumor angiogenesis inhibitor, destabilizes tumor necrosis factor-α mRNA via decreasing nuclear-cytoplasmic translocation of RNA-binding protein HuR

Authors
Zhu, Z., Zhao, Y., Li, J., Tao, L., Shi, P., Wei, Z., Sheng, X., Shen, D., Liu, Z., Zhou, L., Tian, C., Fan, F., Shen, C., Zhu, P., Wang, A., Chen, W., Zhao, Q., Lu, Y.
ID
ZDB-PUB-150828-5
Date
2016
Source
Molecular Carcinogenesis   55(10): 1399-410 (Journal)
Registered Authors
Zhao, Qingshun
Keywords
HuR, angiogenesis, cryptotanshinone, mRNA stability, tumor necrosis factor-α
MeSH Terms
  • Angiogenesis Inhibitors/administration & dosage*
  • Angiogenesis Inhibitors/pharmacology
  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Nucleus/drug effects
  • Cell Nucleus/metabolism
  • Cell Proliferation/drug effects
  • Cytoplasm/drug effects
  • Cytoplasm/metabolism
  • ELAV-Like Protein 1/metabolism*
  • Gene Expression Regulation, Neoplastic/drug effects
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Mice
  • Neoplasms/drug therapy*
  • Phenanthrenes/administration & dosage*
  • Phenanthrenes/pharmacology
  • RNA Stability/drug effects
  • RNA, Messenger/drug effects
  • RNA, Messenger/metabolism
  • Signal Transduction/drug effects
  • Tumor Necrosis Factor-alpha/genetics*
  • Xenograft Model Antitumor Assays
  • Zebrafish
PubMed
26310813 Full text @ Mol. Carcinog.
Abstract
Cryptotanshinone (CT), one major lipophilic component isolated from Salvia miltiorrhiza Bunge, has shown to possess chemopreventive properties against various types of cancer cells. In this study, CT was shown to be a potent anti-angiogenic agent in zebrafish, and mouse models and could limit tumor growth by inhibiting tumor angiogenesis. We further found that CT could inhibit the proliferation, migration, angiogenic sprouting, and tube formation of HUVECs. In addition, we demonstrated that CT could lower the level of TNF-α due to the destabilization of TNF-α mRNA, which associated with regulating 3'-untranslated region (3'-UTR) of TNF-α and preventing the translocation of RNA binding protein, HuR, from the nucleus to the cytoplasm. Moreover, the underlying mechanism responsible for the regulation in angiogenesis by CT was partially related to the suppression of NF-κB, and STAT3 activity. Based on the abilities of CT in targeting tumor cells, inhibiting angiogenesis, and destroying tumor vasculature, CT is worthy of further investigation for preventive, and therapeutic purposes in cancer.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping