{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T23:05:32Z","timestamp":1776121532341,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,7,19]],"date-time":"2016-07-19T00:00:00Z","timestamp":1468886400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["1R01CA093455"],"award-info":[{"award-number":["1R01CA093455"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:p>Pancreatic cancer, the fourth leading cause of cancer death in the United States, has a negative prognosis because metastasis occurs before symptoms manifest. Leiodermatolide, a polyketide macrolide with antimitotic activity isolated from a deep water sponge of the genus <jats:italic>Leiodermatium<\/jats:italic>, exhibits potent and selective cytotoxicity toward the pancreatic cancer cell lines AsPC\u20101, PANC\u20101, BxPC\u20103, and MIA PaCa\u20102, and potent cytotoxicity against skin, breast and colon cancer cell lines. Induction of apoptosis by leiodermatolide was confirmed in the AsPC\u20101, BxPC\u20103 and MIA PaCa\u20102 cells. Leiodermatolide induces cell cycle arrest but has no effects on <jats:italic>in vitro<\/jats:italic> polymerization or depolymerization of tubulin alone, while it enhances polymerization of tubulin containing microtubule associated proteins (MAPs). Observations through confocal microscopy show that leiodermatolide, at low concentrations, causes minimal effects on polymerization or depolymerization of the microtubule network in interphase cells, but disruption of spindle formation in mitotic cells. At higher concentrations, depolymerization of the microtubule network is observed. Visualization of the growing microtubule in HeLa cells expressing GFP\u2010tagged plus end binding protein EB\u20101 showed that leiodermatolide stopped the polymerization of tubulin. These results suggest that leiodermatolide may affect tubulin dynamics without directly interacting with tubulin and hint at a unique mechanism of action. In a mouse model of metastatic pancreatic cancer, leiodermatolide exhibited significant tumor reduction when compared to gemcitabine and controls. The antitumor activities of leiodermatolide, as well as the proven utility of antimitotic compounds against cancer, make leiodermatolide an interesting compound with potential chemotherapeutic effects that may merit further research.<\/jats:p>","DOI":"10.1002\/ijc.30253","type":"journal-article","created":{"date-parts":[[2016,7,4]],"date-time":"2016-07-04T23:47:10Z","timestamp":1467676030000},"page":"2116-2126","source":"Crossref","is-referenced-by-count":28,"title":["Leiodermatolide, a novel marine natural product, has potent cytotoxic and antimitotic activity against cancer cells, appears to affect microtubule dynamics, and exhibits antitumor activity"],"prefix":"10.1002","volume":"139","author":[{"given":"Esther A.","family":"Guzm\u00e1n","sequence":"first","affiliation":[{"name":"Marine Biomedical and Biotechnology Research, Harbor Branch Oceanographic Institute at Florida Atlantic University\u00a0Ft. Pierce  FL 34946"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qunli","family":"Xu","sequence":"additional","affiliation":[{"name":"Eisai Research Institute of Boston Inc Andover MA 01810\u20102441"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tara P.","family":"Pitts","sequence":"additional","affiliation":[{"name":"Marine Biomedical and Biotechnology Research, Harbor Branch Oceanographic Institute at Florida Atlantic University\u00a0Ft. Pierce  FL 34946"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaoru Ogawa","family":"Mitsuhashi","sequence":"additional","affiliation":[{"name":"Eisai Co, Ltd Tsukuba\u2010Shi Ibaraki 300\u20102635 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheryl","family":"Baker","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences University of Central Florida College of Medicine Orlando FL 32827"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia A.","family":"Linley","sequence":"additional","affiliation":[{"name":"Marine Biomedical and Biotechnology Research, Harbor Branch Oceanographic Institute at Florida Atlantic University\u00a0Ft. Pierce  FL 34946"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judy","family":"Oestreicher","sequence":"additional","affiliation":[{"name":"Eisai Research Institute of Boston Inc Andover MA 01810\u20102441"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Tendyke","sequence":"additional","affiliation":[{"name":"Eisai Research Institute of Boston Inc Andover MA 01810\u20102441"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priscilla L.","family":"Winder","sequence":"additional","affiliation":[{"name":"Marine Biomedical and Biotechnology Research, Harbor Branch Oceanographic Institute at Florida Atlantic University\u00a0Ft. Pierce  FL 34946"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward M.","family":"Suh","sequence":"additional","affiliation":[{"name":"Eisai Research Institute of Boston Inc Andover MA 01810\u20102441"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy E.","family":"Wright","sequence":"additional","affiliation":[{"name":"Marine Biomedical and Biotechnology Research, Harbor Branch Oceanographic Institute at Florida Atlantic University\u00a0Ft. Pierce  FL 34946"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,7,19]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"Pancreatic Cancer Canada. The fight to end pancreatic cancer facts you need to know 2015. Available at:http:\/\/www.pancreaticcancercanada.ca\/site\/DocServer\/facts_you_need_to_know.pdf?docID=741. (Accessed on September 06 2016)."},{"key":"e_1_2_6_3_1","unstructured":"American Cancer Society. Cancer Facts and Figures2015. Available at:http:\/\/www.cancer.org\/acs\/groups\/content\/@editorial\/documents\/document\/acspc-044552.pdf. (Accessed on September 06 2016)."},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/np800568j"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-5521(96)90129-5"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3253"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2016.03.056"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0080305"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2016.03.017"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1304369"},{"key":"e_1_2_6_11_1","unstructured":"DimouAT SyrigosKN SaifMW.Novel agents for the treatment of pancreatic adenocarcinoma: any light at the end of the tunnel? Highlights from the \u201c2010 ASCO Annual Meeting\u201d. Chicago IL. June 4\u20108 2010.JOP;11:324\u20137."},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-006-8440-x"},{"key":"e_1_2_6_13_1","first-page":"1057","article-title":"Eribulin, a simplified ketone analog of the tubulin inhibitor halichondrin B, for the potential treatment of cancer","volume":"8","author":"Newman S.","year":"2007","journal-title":"Curr Opin Investig Drugs"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201007719"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-5521(99)80004-0"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200405094"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00600-X"},{"key":"e_1_2_6_18_1","unstructured":"WrightAE ReedJK RobertsJ et al. PCT\/US2007\/017500. Antiproliferative Activity of the Leiodermatolide class of Macrolides.2007."},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja508846g"},{"key":"e_1_2_6_20_1","first-page":"6815","article-title":"Coexistence of high levels of apoptotic signaling and inhibitor of apoptosis proteins in human tumor cells: implication for cancer specific therapy","volume":"63","author":"Yang L","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2044"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1132939"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.91.2.479"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.2144\/000112193"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2009.09.020"},{"key":"e_1_2_6_27_1","first-page":"1604","article-title":"Effect of microtubule\u2010associated proteins on the interaction of vincristine with microtubules and tubulin","volume":"39","author":"Donoso JA","year":"1979","journal-title":"Cancer Res"},{"key":"e_1_2_6_28_1","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1242\/jcs.47.1.237","article-title":"Spirals and paracrystals induced by Vinca alkaloids: evidence that microtubule\u2010associated proteins act as polycations","volume":"47","author":"Haskins KM","year":"1981","journal-title":"J Cell Sci"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2012.61"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201310164"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201206670"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0b013e32831fa39e"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.30253","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.30253","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T11:08:36Z","timestamp":1695553716000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.30253"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,19]]},"references-count":31,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2016,11]]}},"alternative-id":["10.1002\/ijc.30253"],"URL":"https:\/\/doi.org\/10.1002\/ijc.30253","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,19]]}}}