Piperlongumine as a direct TrxR1 inhibitor with suppressive activity against gastric cancer

• Published in: Cancer letters 2016-05, Vol.375 (1), p.114-126
• Main Authors: Zou, Peng, Xia, Yiqun, Ji, Jiansong, Chen, Weiqian, Zhang, Jinsan, Chen, Xi, Rajamanickam, Vinothkumar, Chen, Gaozhi, Wang, Zhe, Chen, Lingfeng, Wang, Yifeng, Yang, Shulin, Liang, Guang
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antioxidants; Apoptosis; Cancer therapies; Cell Line, Tumor; Conflicts of interest; Dioxolanes - pharmacology; Drug resistance; Endoplasmic Reticulum Stress; ER stress; Female; Gastric cancer; Hematology, Oncology and Palliative Medicine; Humans; Membrane Potential, Mitochondrial; Mice, Inbred BALB C; Mice, Nude; Mitochondrial dysfunction; Oxidative stress; Piperlongumine; Protein folding; Proto-Oncogene Proteins c-bcl-2 - metabolism; Reactive oxygen species; Reactive Oxygen Species - metabolism; Stomach Neoplasms - drug therapy; Stomach Neoplasms - pathology; Stress response; Thioredoxin reductase 1; Thioredoxin Reductase 1 - antagonists & inhibitors; Tumor Burden; Tumors; Xenograft Model Antitumor Assays
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2016.02.058

Highlights • Piperlongumine directly binds TrxR1 in vitro and inactivates TrxR1 in human gastric cancer cells. • Stably overexpressing TrxR1 in SGC-7901 cells markedly rescued piperlongumine-induced growth inhibition • Piperlongumine displays synergistic lethality with GSH inhibitors (BSO and Erastin) against gastric cancer cells. • Piperlongumine treatment markedly reduces the TrxR1 activity and tumor cell burden in vivo. • TrxR1 was significantly overexpressed in gastric cancer cell lines and human gastric cancer tissues.