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Enhancement of auranofin-induced apoptosis in MCF-7 human breast cells by selenocystine, a synergistic inhibitor of thioredoxin reductase.
PLoS One. 2013; 8(1):e53945.Plos

Abstract

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

Authors+Show Affiliations

Department of Chemistry, Jinan University, Guangzhou, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23342042

Citation

Liu, Chaoran, et al. "Enhancement of Auranofin-induced Apoptosis in MCF-7 Human Breast Cells By Selenocystine, a Synergistic Inhibitor of Thioredoxin Reductase." PloS One, vol. 8, no. 1, 2013, pp. e53945.
Liu C, Liu Z, Li M, et al. Enhancement of auranofin-induced apoptosis in MCF-7 human breast cells by selenocystine, a synergistic inhibitor of thioredoxin reductase. PLoS ONE. 2013;8(1):e53945.
Liu, C., Liu, Z., Li, M., Li, X., Wong, Y. S., Ngai, S. M., Zheng, W., Zhang, Y., & Chen, T. (2013). Enhancement of auranofin-induced apoptosis in MCF-7 human breast cells by selenocystine, a synergistic inhibitor of thioredoxin reductase. PloS One, 8(1), e53945. https://doi.org/10.1371/journal.pone.0053945
Liu C, et al. Enhancement of Auranofin-induced Apoptosis in MCF-7 Human Breast Cells By Selenocystine, a Synergistic Inhibitor of Thioredoxin Reductase. PLoS ONE. 2013;8(1):e53945. PubMed PMID: 23342042.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhancement of auranofin-induced apoptosis in MCF-7 human breast cells by selenocystine, a synergistic inhibitor of thioredoxin reductase. AU - Liu,Chaoran, AU - Liu,Zhong, AU - Li,Meng, AU - Li,Xiaoling, AU - Wong,Yum-Shing, AU - Ngai,Sai-Ming, AU - Zheng,Wenjie, AU - Zhang,Yibo, AU - Chen,Tianfeng, Y1 - 2013/01/14/ PY - 2012/09/18/received PY - 2012/12/05/accepted PY - 2013/1/24/entrez PY - 2013/1/24/pubmed PY - 2013/7/5/medline SP - e53945 EP - e53945 JF - PloS one JO - PLoS ONE VL - 8 IS - 1 N2 - Thioredoxin system plays an important role in regulation of intracellular redox balance and various signaling pathways. Thioredoxin reductase (TrxR) is overexpressed in many cancer cells and has been identified as a potential target of anticancer drugs. Auranofin (AF) is potent TrxR inhibitor with novel in vitro and in vivo anticancer activities. Selenocystine (SeC) is a nutritionally available selenoamino acid with selective anticancer effects through induction of apoptosis. In the present study, we demonstrated the synergistic effects and the underlying molecular mechanisms of SeC in combination with AF on MCF-7 human breast cancer cells. The results showed that SeC and AF synergistically inhibited the cancer cell growth through induction of ROS-dependent apoptosis with the involvement of mitochondrial dysfunction. DNA damage-mediated p53 phosphorylation and down-regulation of phosphorylated AKT and ERK also contributed to cell apoptosis. Moreover, we demonstrated the important role of TrxR activity in the synergistic action of SeC and AF. Taken together, our results suggest the strategy to use SeC and AF in combination could be a highly efficient way to achieve anticancer synergism by targeting TrxR. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/23342042/Enhancement_of_auranofin_induced_apoptosis_in_MCF_7_human_breast_cells_by_selenocystine_a_synergistic_inhibitor_of_thioredoxin_reductase_ L2 - http://dx.plos.org/10.1371/journal.pone.0053945 DB - PRIME DP - Unbound Medicine ER -