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Microtubules as a target for anticancer drugs
Highly dynamic mitotic-spindle microtubules are among the most successful targets for anticancer therapy, and it is now known that at lower concentrations, microtubule-targeted drugs can suppress micro Tubule dynamics without changingmicrotubule mass; this action leads to mitotic block and apoptosis. Expand
Microtubule-binding agents: a dynamic field of cancer therapeutics
The screening of a range of botanical species and marine organisms has yielded promising new antitubulin agents with novel properties, and the three main objectives are enhanced tumour specificity, reduced neurotoxicity and insensitivity to chemoresistance mechanisms. Expand
Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations.
- M. Jordan, R. Toso, D. Thrower, L. Wilson
- Biology, Medicine
- Proceedings of the National Academy of Sciences…
- 15 October 1993
The results indicate that taxol shares a common antiproliferative mechanism with vinblastine, and at its lowest effective concentrations, taxol appears to block mitosis by kinetically stabilizing spindle microtubules and not by changing the mass of polymerizedmicrotubules. Expand
Effects of vinblastine, podophyllotoxin and nocodazole on mitotic spindles. Implications for the role of microtubule dynamics in mitosis.
The data suggest that these anti-mitotic drugs block mitosis primarily by inhibiting the dynamics of spindle micro Tubules rather than by simply depolymerizing the microtubules. Expand
Taxol suppresses dynamics of individual microtubules in living human tumor cells.
The results indicate that suppression of microtubule dynamics by taxol deleteriously affects the ability of cancer cells to properly assemble a mitotic spindle, pass the metaphase/anaphase checkpoint, and produce progeny. Expand
Mitotic block induced in HeLa cells by low concentrations of paclitaxel (Taxol) results in abnormal mitotic exit and apoptotic cell death.
- M. Jordan, K. Wendell, S. Gardiner, W. B. Derry, H. Copp, L. Wilson
- Biology, Medicine
- Cancer research
- 15 February 1996
The results support the hypothesis that the most potent chemotherapeutic mechanism of paclitaxel is kinetic stabilization of spindle microtubule dynamics. Expand
Mechanism of action of antitumor drugs that interact with microtubules and tubulin.
- M. Jordan
- Current medicinal chemistry. Anti-cancer agents
It can be argued that microtubules represent the single best cancer target identified to date, as considerable evidence indicates that, at lower concentrations, these drugs have a common mechanism of action; they suppress the dynamics of micro Tubulin without appreciably changing the mass of microtubule in the cell. Expand
Substoichiometric binding of taxol suppresses microtubule dynamics.
The data support the hypothesis that binding of a molecule of taxol to a tubulin subunit in microtubules induces a conformational change in that subunit that strongly reduces its ability to dissociate when the subunit becomes exposed at the microtubule end. Expand
Microtubules and actin filaments: dynamic targets for cancer chemotherapy.
By targeting microtubules, drugs inhibit cell proliferation by blocking mitosis at the mitotic checkpoint and inducing apoptosis and the antitumor potential of agents that act on the actin cytoskeleton is outlined. Expand
Mechanism of inhibition of cell proliferation by Vinca alkaloids.
It is suggested that the antiproliferative activity of the Vinca alkaloids at their lowest effective concentrations in HeLa cells is due to inhibition of mitotic spindle function, and that specific alterations of spindle microtubule dynamics appear to differ among the five VincA congeners. Expand