Enhancement of Auranofin-Induced Apoptosis in MCF-7 Human Breast Cells by Selenocystine, a Synergistic Inhibitor of Thioredoxin Reductase

• DOI: 10.1371/journal.pone.0053945
• Publication Date: 2013-01-14T23:28:03Z
• Authors: Chaoran Liu; Zhong Liu; Meng Li; Xiaoling Li; Yum-Shing Wong; Sai-Ming Ngai; Wenjie Zheng; Yibo Zhang; Tianfeng Chen
• Keywords: Auranofin; MCF-7

Thioredoxin system plays an important role in regulation of intracellular redox balance and various signaling pathways. reductase (TrxR) is overexpressed many cancer cells has been identified as a potential target anticancer drugs. Auranofin (AF) potent TrxR inhibitor with novel vitro vivo activities. Selenocystine (SeC) nutritionally available selenoamino acid selective effects through induction apoptosis. In the present study, we demonstrated synergistic underlying molecular mechanisms SeC combination AF on MCF-7 human breast cells. The results showed that synergistically inhibited cell growth ROS-dependent apoptosis involvement mitochondrial dysfunction. DNA damage-mediated p53 phosphorylation down-regulation phosphorylated AKT ERK also contributed to Moreover, activity action AF. Taken together, our suggest strategy use could be highly efficient way achieve synergism by targeting TrxR.