{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:46:45Z","timestamp":1791341205996,"version":"4.3.1"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2005,6,20]],"date-time":"2005-06-20T00:00:00Z","timestamp":1119225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2005,6,20]],"date-time":"2005-06-20T00:00:00Z","timestamp":1119225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pharmacol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Background<\/jats:title>\n                        <jats:p>Anticancer bisdioxopiperazines, including ICRF-154, razoxane (Raz, ICRF-159) and ICRF-193, are a family of anticancer agents developed in the UK, especially targeting metastases of neoplasms. Two other bisdioxopiperazine derivatives, probimane (Pro) and MST-16, were synthesized at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. Cytotoxic activities and mechanisms of Raz (+)-steroisomer (ICRF-187, dexrazoxane), Pro and MST-16 against tumor cells were evaluated by MTT colorimetry, flow cytometry and karyotyping.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>Pro was cytotoxic to human tumor cell lines <jats:italic>in vitro<\/jats:italic> (IC<jats:sub>50<\/jats:sub>&lt;50 \u03bcM for 48 h). Four human tumor cell lines (SCG-7901, K562, A549 and HL60) were susceptible to Pro at low inhibitory concentrations (IC<jats:sub>50<\/jats:sub> values &lt; 10 \u03bcM for 48 h). Although the IC<jats:sub>50<\/jats:sub> against HeLa cell line of vincristine (VCR, 4.56 \u03bcM), doxorubicin (Dox, 1.12 \u03bcM) and 5-fluoruouracil (5-Fu, 0.232 \u03bcM) are lower than Pro (5.12 \u03bcM), ICRF-187 (129 \u03bcM) and MST-16 (26.4 \u03bcM), VCR, Dox and 5-Fu shows a low dose-related \u2013 high cytotoxic activity. Time-response studies showed that the cytotoxic effects of Pro are increased for 3 days in human tumor cells, whereas VCR, Dox and 5-Fu showed decreased cytotoxic action after 24 h. Cell cycle G<jats:sub>2<\/jats:sub>\/M phase arrest and chromosome segregation blocking by Pro and MST-16 were noted. Although there was similar effects of Pro and MST-16 on chromosome segregation blocking action and cell cycle G<jats:sub>2<\/jats:sub>\/M phase arrest at 1- 4 \u03bcM, cytotoxicity of Pro against tumor cells was higher than that of MST-16 <jats:italic>in vitro<\/jats:italic> by a factor of 3- 10 folds. Our data show that Pro may be more effective against lung cancer and leukemia while ICRF-187 and MST-16 shows similar IC<jats:sub>50<\/jats:sub> values only against leukemia.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusion<\/jats:title>\n                        <jats:p>It suggests that Pro has a wider spectrum of cytotoxic effects against human tumor cells than other bisdioxopiperazines, especially against solid tumors, and with a single cytotoxic pathway of Pro and MST-16 affecting chromosome segregation and leading also to cell G<jats:sub>2<\/jats:sub>\/ M phase arrests, which finally reduces cell division rates. Pro may be more potent than MST-16 in cytotoxicity. High dose- and time- responses of Pro, when compared with VCR, 5-Fu and Dox, were seen that suggest a selectivity of Pro against tumor growth. Compounds of bisdioxopiperazines family may keep up their cytotoxic effects longer than many other anticancer drugs.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/1471-2210-5-11","type":"journal-article","created":{"date-parts":[[2005,6,21]],"date-time":"2005-06-21T13:30:13Z","timestamp":1119360613000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Anti-proliferative effects, cell cycle G2\/M phase arrest and blocking of chromosome segregation by probimane and MST-16 in human tumor cell lines"],"prefix":"10.1186","volume":"5","author":[{"given":"Da Yong","family":"Lu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng Hui","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei Yi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao Xin","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li Ping","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin Jiang","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei Hong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong Wen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2005,6,20]]},"reference":[{"key":"93_CR1","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/S1054-3589(08)60025-3","volume":"19","author":"EH Herman","year":"1982","unstructured":"Herman EH, Witiak DT, Hellmann K, Waradek VS: Properties of ICRF-159 and related Bis(dioxopiperazine) compounds. 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