Stabilizing versus Destabilizing the Microtubules: A Double-Edge Sword for an Effective Cancer Treatment Option?
Microtubules are dynamic and structural cellular components involved in several cell functions, including cell shape, motility, and intracellular trafficking. In proliferating cells, they are essential components in the division process through the formation of the mitotic spindle. As a result of th...
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| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Analytical Cellular Pathology |
| Online Access: | http://dx.doi.org/10.1155/2015/690916 |
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| author | Daniele Fanale Giuseppe Bronte Francesco Passiglia Valentina Calò Marta Castiglia Florinda Di Piazza Nadia Barraco Antonina Cangemi Maria Teresa Catarella Lavinia Insalaco Angela Listì Rossella Maragliano Daniela Massihnia Alessandro Perez Francesca Toia Giuseppe Cicero Viviana Bazan |
| author_facet | Daniele Fanale Giuseppe Bronte Francesco Passiglia Valentina Calò Marta Castiglia Florinda Di Piazza Nadia Barraco Antonina Cangemi Maria Teresa Catarella Lavinia Insalaco Angela Listì Rossella Maragliano Daniela Massihnia Alessandro Perez Francesca Toia Giuseppe Cicero Viviana Bazan |
| author_sort | Daniele Fanale |
| collection | DOAJ |
| description | Microtubules are dynamic and structural cellular components involved in several cell functions, including cell shape, motility, and intracellular trafficking. In proliferating cells, they are essential components in the division process through the formation of the mitotic spindle. As a result of these functions, tubulin and microtubules are targets for anticancer agents. Microtubule-targeting agents can be divided into two groups: microtubule-stabilizing, and microtubule-destabilizing agents. The former bind to the tubulin polymer and stabilize microtubules, while the latter bind to the tubulin dimers and destabilize microtubules. Alteration of tubulin-microtubule equilibrium determines the disruption of the mitotic spindle, halting the cell cycle at the metaphase-anaphase transition and, eventually, resulting in cell death. Clinical application of earlier microtubule inhibitors, however, unfortunately showed several limits, such as neurological and bone marrow toxicity and the emergence of drug-resistant tumor cells. Here we review several natural and synthetic microtubule-targeting agents, which showed antitumor activity and increased efficacy in comparison to traditional drugs in various preclinical and clinical studies. Cryptophycins, combretastatins, ombrabulin, soblidotin, D-24851, epothilones and discodermolide were used in clinical trials. Some of them showed antiangiogenic and antivascular activity and others showed the ability to overcome multidrug resistance, supporting their possible use in chemotherapy. |
| format | Article |
| id | doaj-art-47c45085936e40deaa758844f374d87f |
| institution | Kabale University |
| issn | 2210-7177 2210-7185 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Analytical Cellular Pathology |
| spelling | doaj-art-47c45085936e40deaa758844f374d87f2025-02-03T05:47:28ZengWileyAnalytical Cellular Pathology2210-71772210-71852015-01-01201510.1155/2015/690916690916Stabilizing versus Destabilizing the Microtubules: A Double-Edge Sword for an Effective Cancer Treatment Option?Daniele Fanale0Giuseppe Bronte1Francesco Passiglia2Valentina Calò3Marta Castiglia4Florinda Di Piazza5Nadia Barraco6Antonina Cangemi7Maria Teresa Catarella8Lavinia Insalaco9Angela Listì10Rossella Maragliano11Daniela Massihnia12Alessandro Perez13Francesca Toia14Giuseppe Cicero15Viviana Bazan16Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, ItalyDepartment of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, ItalyDepartment of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, ItalyDepartment of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, ItalyDepartment of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, ItalyDepartment of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, ItalyDepartment of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, ItalyDepartment of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, ItalyDepartment of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, ItalyDepartment of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, ItalyDepartment of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, ItalyDepartment of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, ItalyDepartment of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, ItalyDepartment of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, ItalyDepartment of Surgical, Oncological and Oral Sciences, Section of Plastic Surgery, University of Palermo, 90127 Palermo, ItalyDepartment of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, ItalyDepartment of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, ItalyMicrotubules are dynamic and structural cellular components involved in several cell functions, including cell shape, motility, and intracellular trafficking. In proliferating cells, they are essential components in the division process through the formation of the mitotic spindle. As a result of these functions, tubulin and microtubules are targets for anticancer agents. Microtubule-targeting agents can be divided into two groups: microtubule-stabilizing, and microtubule-destabilizing agents. The former bind to the tubulin polymer and stabilize microtubules, while the latter bind to the tubulin dimers and destabilize microtubules. Alteration of tubulin-microtubule equilibrium determines the disruption of the mitotic spindle, halting the cell cycle at the metaphase-anaphase transition and, eventually, resulting in cell death. Clinical application of earlier microtubule inhibitors, however, unfortunately showed several limits, such as neurological and bone marrow toxicity and the emergence of drug-resistant tumor cells. Here we review several natural and synthetic microtubule-targeting agents, which showed antitumor activity and increased efficacy in comparison to traditional drugs in various preclinical and clinical studies. Cryptophycins, combretastatins, ombrabulin, soblidotin, D-24851, epothilones and discodermolide were used in clinical trials. Some of them showed antiangiogenic and antivascular activity and others showed the ability to overcome multidrug resistance, supporting their possible use in chemotherapy.http://dx.doi.org/10.1155/2015/690916 |
| spellingShingle | Daniele Fanale Giuseppe Bronte Francesco Passiglia Valentina Calò Marta Castiglia Florinda Di Piazza Nadia Barraco Antonina Cangemi Maria Teresa Catarella Lavinia Insalaco Angela Listì Rossella Maragliano Daniela Massihnia Alessandro Perez Francesca Toia Giuseppe Cicero Viviana Bazan Stabilizing versus Destabilizing the Microtubules: A Double-Edge Sword for an Effective Cancer Treatment Option? Analytical Cellular Pathology |
| title | Stabilizing versus Destabilizing the Microtubules: A Double-Edge Sword for an Effective Cancer Treatment Option? |
| title_full | Stabilizing versus Destabilizing the Microtubules: A Double-Edge Sword for an Effective Cancer Treatment Option? |
| title_fullStr | Stabilizing versus Destabilizing the Microtubules: A Double-Edge Sword for an Effective Cancer Treatment Option? |
| title_full_unstemmed | Stabilizing versus Destabilizing the Microtubules: A Double-Edge Sword for an Effective Cancer Treatment Option? |
| title_short | Stabilizing versus Destabilizing the Microtubules: A Double-Edge Sword for an Effective Cancer Treatment Option? |
| title_sort | stabilizing versus destabilizing the microtubules a double edge sword for an effective cancer treatment option |
| url | http://dx.doi.org/10.1155/2015/690916 |
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