{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T18:58:04Z","timestamp":1773860284482,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":2830,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2001,5]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Recently discovered chemically modified tetracyclines (CMTs) have shown <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> anti\u2010proliferative and anti\u2010tumour activities. Here, we evaluated <jats:italic>in vitro<\/jats:italic> the anti\u2010proliferative and apoptotic activity of six different dedimethylamino chemically modified tetracyclines (CMT\u20101, CMT\u20103, CMT\u20105, CMT\u20106, CMT\u20107 and CMT\u20108) in sensitive and multidrug resistant myeloid leukaemia cells (HL60 and HL60R) <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Three of these compounds (CMT\u20105, CMT\u20106, CMT\u20107) showed low cytotoxic activity both in sensitive and in resistant cells, CMT\u20103 was endowed with a high anti\u2010proliferative activity only in sensitive cells and was moderately effective as apoptosis inducing agent, with an activity similar to that shown by doxycycline. On the contrary, CMT\u20101 and CMT\u20108 were very effective as programmed cell death inducing agents.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The apoptotic pathway activated by these compounds involved the activation of caspases, especially caspase\u20109 and, for CMT\u20101, also the activation of Fas.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Interestingly CMT\u20108, but not CMT\u20101, was able to induce apoptosis in multidrug resistant HL60R and in Fas\u2010ligand resistant HUT78B1 cell lines. These properties, together with others previously described (e.g. anti\u2010metastatic and anti\u2010osteolytic activities), suggest that CMT\u20108 may have important applications in the clinical management of cancer.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The comparative analysis of structure\u2010activity relationship of CMT\u20108 and doxycycline suggests that the C\u20105 hydroxy moiety may play an important role in conferring activity in multidrug resistant cells. These findings appear to support the hypothesis that CMT\u20108 may represent an interesting lead for the development of a new class of potent apoptosis inducer agents active in multidrug resistant and Fas\u2010ligand resistant malignancies.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2001) <jats:bold>133<\/jats:bold>, 306\u2013314; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0704068\">10.1038\/sj.bjp.0704068<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0704068","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T21:25:23Z","timestamp":1106947523000},"page":"306-314","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Effects of chemically modified tetracyclines (CMTs) in sensitive, multidrug resistant and apoptosis resistant leukaemia cell lines"],"prefix":"10.1111","volume":"133","author":[{"given":"Manlio","family":"Tolomeo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Grimaudo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Milano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marzia","family":"La Rosa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viviana","family":"Ferlazzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria","family":"Di Bella","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caterina","family":"Barbera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Simoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pietro","family":"D'Agostino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Cillari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0065-2571(94)00022-U"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/08959374980120010701"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1042\/bst0220055"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(98)00046-6"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1086\/517383"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.990130802"},{"key":"e_1_2_7_8_1","volume-title":"Current Protocols in Immunology","author":"DUKE R.C.","year":"1992"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb07763.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.3.935.935_935_943"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.1988.tb01418.x"},{"key":"e_1_2_7_12_1","first-page":"407","article-title":"Effects of doxycycline on in vitro growth, migration, and gelatinase activity of breast carcinoma cells","volume":"125","author":"FIFE R.","year":"1995","journal-title":"J. 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