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These tumor\u2010specific conditions, especially glucose deprivation, activate a signaling pathway called the unfolded protein response (UPR), which enhances cell survival by induction of the stress proteins. We have established a screening method to discover anticancer agents that could preferentially inhibit tumor cell viability under glucose\u2010deprived conditions. Here we identify arctigenin (ARC\u2010G) as an active compound that shows selective cytotoxicity and inhibits the UPR during glucose deprivation. Indeed, ARC\u2010G blocked expression of UPR target genes such as phosphorylated\u2010PERK, ATF4, CHOP, and GRP78, which was accompanied by enhanced phosphorylation of eIF2\u03b1 during glucose deprivation. The UPR inhibition led to apoptosis involving a mitochondrial pathway by activation of caspase\u20109 and \u20103. Furthermore, ARC\u2010G suppressed tumor growth of colon cancer HT\u201029 xenografts. Our results demonstrate that ARC\u2010G can be served as a novel type of antitumor agent targeting the UPR in glucose\u2010deprived solid tumors. J. Cell. Physiol. 224:33\u201340, 2010 \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.22085","type":"journal-article","created":{"date-parts":[[2010,3,15]],"date-time":"2010-03-15T15:09:41Z","timestamp":1268665781000},"page":"33-40","source":"Crossref","is-referenced-by-count":59,"title":["Arctigenin blocks the unfolded protein response and shows therapeutic antitumor 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