title: Cryptotanshinone, a novel tumor angiogenesis inhibitor, destabilizes tumor necrosis factor-α mRNA via decreasing nuclear-cytoplasmic translocation of RNA-binding protein HuR.
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. © 2015 Wiley Periodicals, Inc.
authors: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors: Zhijie
authors: Z
authors: Zhu
authors: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors: Yang
authors: Y
authors: Zhao
authors: Model Animal Research Center of Nanjing University, Nanjing, 210061, China.
authors: Junbo
authors: J
authors: Li
authors: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors: Li
authors: L
authors: Tao
authors: Model Animal Research Center of Nanjing University, Nanjing, 210061, China.
authors: Peiliang
authors: P
authors: Shi
authors: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors: Zhonghong
authors: Z
authors: Wei
authors: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors: Xiaobo
authors: X
authors: Sheng
authors: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors: Dandan
authors: D
authors: Shen
authors: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors: Zhaoguo
authors: Z
authors: Liu
authors: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors: Liang
authors: L
authors: Zhou
authors: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors: Chao
authors: C
authors: Tian
authors: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors: Fangtian
authors: F
authors: Fan
authors: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors: Cunsi
authors: C
authors: Shen
authors: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors: Pingting
authors: P
authors: Zhu
authors: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors: Aiyun
authors: A
authors: Wang
authors: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China.|Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors: Wenxing
authors: W
authors: Chen
authors: Model Animal Research Center of Nanjing University, Nanjing, 210061, China.
authors: Qingshun
authors: Q
authors: Zhao
authors: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China. profyinlu@163.com.|Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China. profyinlu@163.com.|Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China. profyinlu@163.com.
authors: Yin
authors: Y
authors: Lu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D000067780:ELAV-Like Protein 1 / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D010616:Phenanthrenes / Q000008:administration & dosage* / Q000494:pharmacology; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays; D015027:Zebrafish
chemical_list: D020533:Angiogenesis Inhibitors; D000067780:ELAV-Like Protein 1; D010616:Phenanthrenes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C037886:cryptotanshinone
keywords: HuR; angiogenesis; cryptotanshinone; mRNA stability; tumor necrosis factor-α