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Leukemia\nrelapse is due to residual quiescent leukemia cells that escape conventional\ntherapies and later reemerge. Eliminating not only growing but quiescent\nleukemia cells is critical to effectively treating leukemia and preventing its\nrecurrence. Such dual targeting therapeutic agents, however, are lacking in the\nclinic. To start tackling this problem, encouraged by the promising anticancer\neffects of a set of curcumin derivatives in our earlier studies, we examined in\nthis work the effects of a 4-arylmethyl curcumin derivative (C212) in\neliminating both growing and quiescent leukemia cells.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>We analyzed the effects of C212 on the growth and viability of\ngrowing and quiescent leukemia cells using MTS, apoptosis, cell cycle and cell\ntracking assays. The effects of C212 on the quiescence depth of leukemia cells\nwere measured using EdU incorporation assay upon growth stimulation. The\nmechanisms of C212-induced apoptosis and deep dormancy, particularly associated\nwith its inhibition of Hsp90 activity, were studied using molecular docking,\nprotein aggregation assay, and Western blot of client proteins.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>C212, on the one hand, inhibits growing leukemia cells at a higher\nefficacy than curcumin by inducing apoptosis and G2\/M accumulation; it, on the\nother hand, eliminates quiescent leukemia cells that are resistant to\nconventional treatments. Furthermore, C212 drives leukemia cells into and kills\nthem at deep quiescence. Lastly, we show that C212 induces apoptosis and drives\ncells into deep dormancy at least partially by binding to and inhibiting Hsp90,\nleading to client protein degradation and protein aggregation.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>C212 effectively eliminates both growing and quiescent leukemia\ncells by inhibiting Hsp90. The property of C212 to kill quiescent leukemia cells\nin deep dormancy avoids the risk associated with awaking therapy-resistant\nsubpopulation of quiescent leukemia cells during treatments, which may lead to\nthe development of novel therapies against leukemia relapse.<\/jats:p>\n\n<\/jats:sec>","DOI":"10.1186\/s12964-020-00652-4","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T10:04:21Z","timestamp":1601373861000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Curcumin derivative C212 inhibits Hsp90 and\neliminates both growing and quiescent leukemia cells in deep dormancy"],"prefix":"10.1186","volume":"18","author":[{"given":"Bi","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunzhu","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huafang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimiko Della","family":"Croce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjuan","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0167-777X","authenticated-orcid":false,"given":"Guang","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,29]]},"reference":[{"key":"652_CR1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.tox.2010.03.012","volume":"271","author":"R L\u00fcpertz","year":"2010","unstructured":"L\u00fcpertz R, W\u00e4tjen W, Kahl R, Chovolou Y. 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