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C1, a highly potent novel curcumin derivative, binds to tubulin, disrupts microtubule network and induces apoptosis
We have synthesized a curcumin derivative, 4-{5-(4-hydroxy-3-methoxy-phenyl)-2-[3-(4-hydroxy-3-methoxy-phenyl)-acryloyl]-3-oxo-penta-1,4-dienyl}-piperidine-1-carboxylic acid tert-butyl ester (C1) that displays much stronger antiproliferative activity against various types of cancer cells including m...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847174/ https://www.ncbi.nlm.nih.gov/pubmed/26980197 http://dx.doi.org/10.1042/BSR20160039 |
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author | Srivastava, Shalini Mishra, Satyendra Surolia, Avadhesha Panda, Dulal |
author_facet | Srivastava, Shalini Mishra, Satyendra Surolia, Avadhesha Panda, Dulal |
author_sort | Srivastava, Shalini |
collection | PubMed |
description | We have synthesized a curcumin derivative, 4-{5-(4-hydroxy-3-methoxy-phenyl)-2-[3-(4-hydroxy-3-methoxy-phenyl)-acryloyl]-3-oxo-penta-1,4-dienyl}-piperidine-1-carboxylic acid tert-butyl ester (C1) that displays much stronger antiproliferative activity against various types of cancer cells including multidrug resistance cells than curcumin. C1 depolymerized both interphase and mitotic microtubules in MCF-7 cells and also inhibited the reassembly of microtubules in these cells. C1 inhibited the polymerization of purified tubulin, disrupted the lattice structure of microtubules and suppressed their GTPase activity in vitro. The compound bound to tubulin with a dissociation constant of 2.8±1 μM and perturbed the secondary structures of tubulin. Further, C1 treatment reduced the expression of Bcl2, increased the expression of Bax and down regulated the level of a key regulator of p53, murine double minute 2 (Mdm2) (S166), in MCF-7 cells. C1 appeared to induce p53 mediated apoptosis in MCF-7 cells. Interestingly, C1 showed more stability in aqueous buffer than curcumin. The results together showed that C1 perturbed microtubule network and inhibited cancer cells proliferation more efficiently than curcumin. The strong antiproliferative activity and improved stability of C1 indicated that the compound may have a potential as an anticancer agent. |
format | Online Article Text |
id | pubmed-4847174 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-48471742016-05-09 C1, a highly potent novel curcumin derivative, binds to tubulin, disrupts microtubule network and induces apoptosis Srivastava, Shalini Mishra, Satyendra Surolia, Avadhesha Panda, Dulal Biosci Rep Original Papers We have synthesized a curcumin derivative, 4-{5-(4-hydroxy-3-methoxy-phenyl)-2-[3-(4-hydroxy-3-methoxy-phenyl)-acryloyl]-3-oxo-penta-1,4-dienyl}-piperidine-1-carboxylic acid tert-butyl ester (C1) that displays much stronger antiproliferative activity against various types of cancer cells including multidrug resistance cells than curcumin. C1 depolymerized both interphase and mitotic microtubules in MCF-7 cells and also inhibited the reassembly of microtubules in these cells. C1 inhibited the polymerization of purified tubulin, disrupted the lattice structure of microtubules and suppressed their GTPase activity in vitro. The compound bound to tubulin with a dissociation constant of 2.8±1 μM and perturbed the secondary structures of tubulin. Further, C1 treatment reduced the expression of Bcl2, increased the expression of Bax and down regulated the level of a key regulator of p53, murine double minute 2 (Mdm2) (S166), in MCF-7 cells. C1 appeared to induce p53 mediated apoptosis in MCF-7 cells. Interestingly, C1 showed more stability in aqueous buffer than curcumin. The results together showed that C1 perturbed microtubule network and inhibited cancer cells proliferation more efficiently than curcumin. The strong antiproliferative activity and improved stability of C1 indicated that the compound may have a potential as an anticancer agent. Portland Press Ltd. 2016-04-27 /pmc/articles/PMC4847174/ /pubmed/26980197 http://dx.doi.org/10.1042/BSR20160039 Text en © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution Licence 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Papers Srivastava, Shalini Mishra, Satyendra Surolia, Avadhesha Panda, Dulal C1, a highly potent novel curcumin derivative, binds to tubulin, disrupts microtubule network and induces apoptosis |
title | C1, a highly potent novel curcumin derivative, binds to tubulin, disrupts microtubule network and induces apoptosis |
title_full | C1, a highly potent novel curcumin derivative, binds to tubulin, disrupts microtubule network and induces apoptosis |
title_fullStr | C1, a highly potent novel curcumin derivative, binds to tubulin, disrupts microtubule network and induces apoptosis |
title_full_unstemmed | C1, a highly potent novel curcumin derivative, binds to tubulin, disrupts microtubule network and induces apoptosis |
title_short | C1, a highly potent novel curcumin derivative, binds to tubulin, disrupts microtubule network and induces apoptosis |
title_sort | c1, a highly potent novel curcumin derivative, binds to tubulin, disrupts microtubule network and induces apoptosis |
topic | Original Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847174/ https://www.ncbi.nlm.nih.gov/pubmed/26980197 http://dx.doi.org/10.1042/BSR20160039 |
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