Author: Wang, Le ; Duan, Dongzhu ; Xiao, Jian ; Jin, Xiaojie ; Yan, Yunyun ; Tian, Jingjing ; Guo, Xiangyu ; Li, Mi ; Wang, Zihua ; Song, Peng ; Wang, Xiaoling

Aberrant activation of thioredoxin reductase (TrxR) is correlated with tumor occurrence and progression, suggesting that TrxR inhibitors can be used as antitumor agents. In this study, we evaluated the anticancer efficacy of eupalinilides B on colorectal cancer cells. Eupalinilides B primarily targeted the conserved selenocysteine 498 residues in TrxR. Besides, it inhibited the enzyme activity in an irreversible manner. After eupalinilides B was used to pharmacologically inhibit TrxR, reactive oxygen species accumulated, and the intracellular redox balance was broken, finally causing oxidative stress-induced tumor cell apoptosis. Significantly, eupalinilides B treatment inhibited in vivo tumor growth. Targeting TrxR by eupalinilides B reveals the new mechanism underlying eupalinilides B and provides insight in developing eupalinilides B as the candidate antitumor chemotherapeutic agent for the treatment of cancer.

01 Nov 2014·Biochimica et Biophysica Acta (BBA) - General Subjects

Selenoproteins and selenium status in bone physiology and pathology

Review

Author: Zhang, Zhichao ; Xiao, Jianru ; Zhang, Jinsong

BACKGROUNDEmerging evidence supports the view that selenoproteins are essential for maintaining bone health.SCOPE OF REVIEWThe current state of knowledge concerning selenoproteins and Se status in bone physiology and pathology is summarized.MAJOR CONCLUSIONSAntioxidant selenoproteins including glutathione peroxidase (GPx) and thioredoxin reductase (TrxR), as a whole, play a pivotal role in maintaining bone homeostasis and protecting against bone loss. GPx1, a major antioxidant enzyme in osteoclasts, is up-regulated by estrogen, an endogenous inhibitor of osteoclastogenesis. TrxR1 is an immediate early gene in response to 1α,25-dihydroxyvitamin D3, an osteoblastic differentiation agent. The combination of 1α,25-dihydroxyvitamin D3 and Se generates a synergistic elevation of TrxR activity in Se-deficient osteoblasts. Of particular concern, pleiotropic TrxR1 is implicated in promoting NFκB activation. Coincidentally, TrxR inhibitors such as curcumin and gold compounds exhibit potent osteoclastogenesis inhibitory activity. Studies in patients with the mutations of selenocysteine insertion sequence-binding protein 2, a key trans-acting factor for the co-translational insertion of selenocysteine into selenoproteins have clearly established a causal link of selenoproteins in bone development. Se transport to bone relies on selenoprotein P. Plasma selenoprotein P concentrations have been found to be positively correlated with bone mineral density in elderly women.GENERAL SIGNIFICANCEA full understanding of the role and function of selenoproteins and Se status on bone physiology and pathology may lead to effectively prevent against or modify bone diseases by using Se.

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Preclinical	CN	Lanzhou University	26 Jun 2014

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