Hua S.-C.TIEN-CHUN CHANGChen H.-R.Lu C.-H.Liu Y.-W.Chen S.-H.Yu H.-I.Chang Y.-P.Lee Y.-R.2020-06-032020-06-0320120724-8741https://www.scopus.com/inward/record.uri?eid=2-s2.0-84862635118&doi=10.1007%2fs11095-012-0727-3&partnerID=40&md5=91c9ec843c8c26ff2724b74ec04e139fhttps://scholars.lib.ntu.edu.tw/handle/123456789/496610Purpose: A novel and effective treatment is urgently needed to deal with the current treatment dilemma in incurable differentiated thyroid cancer (DTC), poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC). Reversine, a small synthetic purine analogue (2,6-disubstituted purine), has been shown to be effective in tumor suppression. Methods: We performed in vitro evaluation of anti-tumor effects of reversine on proliferation, cell cycle, and apoptosis in human PDTC, ATC, and follicular thyroid cancer cell lines, respectively. Results: Treatment of these three lines with reversine inhibited proliferation in a time- and dose-dependent manner. G2/M accumulation was demonstrated in cell cycle analysis. Reversine induced apoptosis in PDTC cells with caspase-3 and caspase-8 activation, but not caspase-9. Use of a pan-caspase inhibitor before treatment with reversine attenuated cell death. Reversine also showed in vivo growth inhibitory effects on ATC cells in a xenograft nude mice model. Conclusions: Data demonstrated that reversine is effective in inhibiting the growth of thyroid cancer cells by cell cycle arrest or apoptosis, especially with the more aggressive ATC and PDTC. Apoptosis was induced by the mitochondria-independent pathway. Reversine is therefore worthy of further investigation in clinical therapeutics. ? 2012 Springer Science+Business Media, LLC.[SDGs]SDG3antineoplastic agent; caspase 3; caspase 8; caspase 9; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; purine derivative; reversine; unclassified drug; animal experiment; animal model; antineoplastic activity; apoptosis; article; cancer cell; cancer inhibition; cell cycle; cell cycle arrest; cell differentiation; cell proliferation; controlled study; differentiated thyroid cancer; dose time effect relation; drug efficacy; drug inhibition; drug screening; enzyme activation; G2 phase cell cycle checkpoint; human; human cell; in vitro study; M phase cell cycle checkpoint; male; mouse; nonhuman; poorly differentiated thyroid cancer; priority journal; thyroid follicular carcinoma; tumor xenograft; Animals; Antineoplastic Agents; Apoptosis; Caspase 3; Caspase 8; Caspase 9; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Purines; Thyroid Gland; Thyroid Neoplasmsjournal article10.1007/s11095-012-0727-3224770672-s2.0-84862635118