Stabilizing versus destabilizing the microtubules: A double-edge sword for an effective cancer treatment option?

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Abstract

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.
Lingua originaleEnglish
Numero di pagine19
RivistaAnalytical Cellular Pathology
Volume2015
Stato di pubblicazionePublished - 2015

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Microtubules
Neoplasms
Tubulin
Therapeutics
Spindle Apparatus
Epothilones
Depsipeptides
Anaphase
Cell Shape
Multiple Drug Resistance
Cellular Structures
Metaphase
Drug-Related Side Effects and Adverse Reactions
Antineoplastic Agents
Cell Movement
Cell Cycle
Polymers
Cell Death
Bone Marrow
Clinical Trials

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Medicine
  • Cell Biology
  • Cancer Research

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title = "Stabilizing versus destabilizing the microtubules: A double-edge sword for an effective cancer treatment option?",
abstract = "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.",
author = "Marta Castiglia and Nadia Barraco and Antonina Cangemi and Valentina Calo' and Daniela Massihnia and Angela Listi' and Daniele Fanale and Francesco Passiglia and Francesca Toia and Giuseppe Cicero and Giuseppe Bronte and Alessandro Perez and Viviana Bazan and {Di Piazza}, Florinda and Lavinia Insalaco and Catarella, {Maria Teresa}",
year = "2015",
language = "English",
volume = "2015",
journal = "Analytical Cellular Pathology",
issn = "2210-7177",
publisher = "IOS Press",

}

TY - JOUR

T1 - Stabilizing versus destabilizing the microtubules: A double-edge sword for an effective cancer treatment option?

AU - Castiglia, Marta

AU - Barraco, Nadia

AU - Cangemi, Antonina

AU - Calo', Valentina

AU - Massihnia, Daniela

AU - Listi', Angela

AU - Fanale, Daniele

AU - Passiglia, Francesco

AU - Toia, Francesca

AU - Cicero, Giuseppe

AU - Bronte, Giuseppe

AU - Perez, Alessandro

AU - Bazan, Viviana

AU - Di Piazza, Florinda

AU - Insalaco, Lavinia

AU - Catarella, Maria Teresa

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

UR - http://hdl.handle.net/10447/152042

UR - http://www.hindawi.com/journals/acp/

M3 - Article

VL - 2015

JO - Analytical Cellular Pathology

JF - Analytical Cellular Pathology

SN - 2210-7177

ER -