Scientific Reports (Jul 2017)

Selenocysteine induces apoptosis in human glioma cells: evidence for TrxR1-targeted inhibition and signaling crosstalk

  • Cun-dong Fan,
  • Xiao-yan Fu,
  • Zong-yong Zhang,
  • Ming-zhi Cao,
  • Jing-yi Sun,
  • Ming-feng Yang,
  • Xiao-ting Fu,
  • Shi-jun Zhao,
  • Lu-rong Shao,
  • Hui-fang Zhang,
  • Xiao-yi Yang,
  • Bao-liang Sun

DOI
https://doi.org/10.1038/s41598-017-06979-2
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 11

Abstract

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Abstract Thioredoxin reductase (TrxR) as a selenium (Se)-containing antioxidase plays key role in regulating intracellular redox status. Selenocystine (SeC) a natural available Se-containing amino acid showed novel anticancer potential through triggering oxidative damage-mediated apoptosis. However, whether TrxR-mediated oxidative damage was involved in SeC-induced apoptosis in human glioma cells has not been elucidated yet. Herein, SeC-induced human glioma cell apoptosis was detected in vitro, accompanied by PARP cleavage, caspases activation and DNA fragmentation. Mechanically, SeC caused mitochondrial dysfunction and imbalance of Bcl-2 family expression. SeC treatment also triggered ROS-mediated DNA damage and disturbed the MAPKs and AKT pathways. However, inhibition of ROS overproduction effectively attenuated SeC-induced oxidative damage and apoptosis, and normalized the expression of MAPKs and AKT pathways, indicating the significance of ROS in SeC-induced apoptosis. Importantly, U251 human glioma xenograft growth in nude mice was significantly inhibited in vivo. Further investigation revealed that SeC-induced oxidative damage was achieved by TrxR1-targeted inhibition in vitro and in vivo. Our findings validated the potential of SeC to inhibit human glioma growth by oxidative damage-mediated apoptosis through triggering TrxR1-targeted inhibition.