A novel microtubule inhibitor 4SC-207 with anti-proliferative activity in taxane-resistant cells.
Microtubule inhibitors are invaluable tools in cancer chemotherapy: taxanes and vinca alkaloids have been successfully used in the clinic over the past thirty years against a broad range of tumors. However, two factors have limited the effectiveness of microtubule inhibitors: toxicity and resistance...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3855670?pdf=render |
| _version_ | 1819213300376797184 |
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| author | Elena Bausch Hella Kohlhof Svetlana Hamm Rolf Krauss Roland Baumgartner Lucia Sironi |
| author_facet | Elena Bausch Hella Kohlhof Svetlana Hamm Rolf Krauss Roland Baumgartner Lucia Sironi |
| author_sort | Elena Bausch |
| collection | DOAJ |
| description | Microtubule inhibitors are invaluable tools in cancer chemotherapy: taxanes and vinca alkaloids have been successfully used in the clinic over the past thirty years against a broad range of tumors. However, two factors have limited the effectiveness of microtubule inhibitors: toxicity and resistance. In particular, the latter is highly unpredictable, variable from patient to patient and is believed to be the cause of treatment failure in most cases of metastatic cancers. For these reasons, there is an increasing demand for new microtubule inhibitors that can overcome resistance mechanisms and that, at the same time, have reduced side effects. Here we present a novel microtubule inhibitor, 4SC-207, which shows strong anti-proliferative activity in a large panel of tumor cell lines with an average GI50 of 11 nM. In particular, 4SC-207 is active in multi-drug resistant cell lines, such as HCT-15 and ACHN, suggesting that it is a poor substrate for drug efflux pumps. 4SC-207 inhibits microtubule growth in vitro and in vivo and promotes, in a dose dependent manner, a mitotic delay/arrest, followed by apoptosis or aberrant divisions due to chromosome alignment defects and formation of multi-polar spindles. Furthermore, preliminary data from preclinical studies suggest low propensity towards bone marrow toxicities at concentrations that inhibit tumor growth in paclitaxel-resistant xenograft models. In summary, our results suggest that 4SC-207 may be a potential anti-cancer agent. |
| first_indexed | 2024-12-23T06:56:40Z |
| format | Article |
| id | doaj.art-887fcc1da8cb4265aa3d55d61a7da24a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T06:56:40Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-887fcc1da8cb4265aa3d55d61a7da24a2022-12-21T17:56:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01811e7959410.1371/journal.pone.0079594A novel microtubule inhibitor 4SC-207 with anti-proliferative activity in taxane-resistant cells.Elena BauschHella KohlhofSvetlana HammRolf KraussRoland BaumgartnerLucia SironiMicrotubule inhibitors are invaluable tools in cancer chemotherapy: taxanes and vinca alkaloids have been successfully used in the clinic over the past thirty years against a broad range of tumors. However, two factors have limited the effectiveness of microtubule inhibitors: toxicity and resistance. In particular, the latter is highly unpredictable, variable from patient to patient and is believed to be the cause of treatment failure in most cases of metastatic cancers. For these reasons, there is an increasing demand for new microtubule inhibitors that can overcome resistance mechanisms and that, at the same time, have reduced side effects. Here we present a novel microtubule inhibitor, 4SC-207, which shows strong anti-proliferative activity in a large panel of tumor cell lines with an average GI50 of 11 nM. In particular, 4SC-207 is active in multi-drug resistant cell lines, such as HCT-15 and ACHN, suggesting that it is a poor substrate for drug efflux pumps. 4SC-207 inhibits microtubule growth in vitro and in vivo and promotes, in a dose dependent manner, a mitotic delay/arrest, followed by apoptosis or aberrant divisions due to chromosome alignment defects and formation of multi-polar spindles. Furthermore, preliminary data from preclinical studies suggest low propensity towards bone marrow toxicities at concentrations that inhibit tumor growth in paclitaxel-resistant xenograft models. In summary, our results suggest that 4SC-207 may be a potential anti-cancer agent.http://europepmc.org/articles/PMC3855670?pdf=render |
| spellingShingle | Elena Bausch Hella Kohlhof Svetlana Hamm Rolf Krauss Roland Baumgartner Lucia Sironi A novel microtubule inhibitor 4SC-207 with anti-proliferative activity in taxane-resistant cells. PLoS ONE |
| title | A novel microtubule inhibitor 4SC-207 with anti-proliferative activity in taxane-resistant cells. |
| title_full | A novel microtubule inhibitor 4SC-207 with anti-proliferative activity in taxane-resistant cells. |
| title_fullStr | A novel microtubule inhibitor 4SC-207 with anti-proliferative activity in taxane-resistant cells. |
| title_full_unstemmed | A novel microtubule inhibitor 4SC-207 with anti-proliferative activity in taxane-resistant cells. |
| title_short | A novel microtubule inhibitor 4SC-207 with anti-proliferative activity in taxane-resistant cells. |
| title_sort | novel microtubule inhibitor 4sc 207 with anti proliferative activity in taxane resistant cells |
| url | http://europepmc.org/articles/PMC3855670?pdf=render |
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