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Cryptotanshinone, a novel tumor angiogenesis inhibitor, destabilizes tumor necrosis factor‐α mRNA via decreasing nuclear–cytoplasmic translocation of RNA‐binding protein HuR
Author(s) -
Zhu Zhijie,
Zhao Yang,
Li Junbo,
Tao Li,
Shi Peiliang,
Wei Zhonghong,
Sheng Xiaobo,
Shen Dandan,
Liu Zhaoguo,
Zhou Liang,
Tian Chao,
Fan Fangtian,
Shen Cunsi,
Zhu Pingting,
Wang Aiyun,
Chen Wenxing,
Zhao Qingshun,
Lu Yin
Publication year - 2016
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22383
Subject(s) - angiogenesis , biology , untranslated region , rna binding protein , tumor necrosis factor alpha , salvia miltiorrhiza , cancer research , messenger rna , zebrafish , rna , cytoplasm , chromosomal translocation , microbiology and biotechnology , biochemistry , immunology , gene , pathology , medicine , alternative medicine , traditional chinese medicine
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. © 2015 Wiley Periodicals, Inc.